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Soriano-Cruz M, Vázquez-González WG, Molina-Vargas P, Faustino-Trejo A, Chávez-Rueda AK, Legorreta-Haquet MV, Aguilar-Ruíz SR, Chávez-Sánchez L. Exosomes as Regulators of Macrophages in Cardiovascular Diseases. Biomedicines 2024; 12:2683. [PMID: 39767590 PMCID: PMC11726971 DOI: 10.3390/biomedicines12122683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Revised: 11/17/2024] [Accepted: 11/18/2024] [Indexed: 01/16/2025] Open
Abstract
Macrophages in atherosclerosis and myocardial infarction have diverse functions, such as foam cell formation and the induction of an inflammatory response that promotes ventricular dysfunction in the heart. Exosomes are small vesicles released by many different types of cells, such as macrophages, dendritic cells, platelets and other immunoregulatory cells, that facilitate communication with other cells, modulating the biological functions of recipient cells. Exosomes offer a novel therapeutic approach for the polarization of macrophages involved in cardiovascular diseases. In this review, we provide an overview of the biological role of macrophages in atherosclerosis and myocardial infarction and the effects of exosomes on these cells as therapeutic agents in the disease.
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Affiliation(s)
- Marina Soriano-Cruz
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
- Unidad de Investigación Médica en Enfermedades Metabólicas, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
- Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca 68020, Mexico
| | - Wendy Guadalupe Vázquez-González
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
| | - Paula Molina-Vargas
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
- Unidad de Investigación Médica en Enfermedades Metabólicas, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
| | - Alejandro Faustino-Trejo
- Unidad de Investigación Médica en Enfermedades Metabólicas, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
| | - Adriana Karina Chávez-Rueda
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
| | - María Victoria Legorreta-Haquet
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
| | | | - Luis Chávez-Sánchez
- Unidad de Investigación Médica en Inmunología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico; (M.S.-C.); (W.G.V.-G.)
- Unidad de Investigación Médica en Enfermedades Metabólicas, Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
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Liu W, Li N, Hou J, Cao R, Jia L, Guo Y, Xu J. Structure and antitumor activity of a polysaccharide from Rosa roxburghii. Int J Biol Macromol 2024; 273:132807. [PMID: 38825289 DOI: 10.1016/j.ijbiomac.2024.132807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 05/14/2024] [Accepted: 05/30/2024] [Indexed: 06/04/2024]
Abstract
It is well known that Rosa roxburghii, as a homology of both medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80-1). RRTP80-1 was measured to have an average molecular weight of 8.65 × 103 g/mol. Monosaccharide composition analysis revealed that RRTP80-1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Methylation and GC-MS analysis suggested that the backbone of RRTP80-1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-β-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains composed of α-l-Araf-(1→. In vivo studies indicated that RRTP80-1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80-1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80-1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80-1 in cancer treatment was preliminarily clarified in this study.
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Affiliation(s)
- Wenhui Liu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China
| | - Na Li
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China
| | - Jiantong Hou
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China
| | - Ruyu Cao
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China
| | - Lingyun Jia
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
| | - Yuanqiang Guo
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
| | - Jing Xu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, People's Republic of China.
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Lusta KA, Summerhill VI, Khotina VA, Sukhorukov VN, Glanz VY, Orekhov AN. The Role of Bacterial Extracellular Membrane Nanovesicles in Atherosclerosis: Unraveling a Potential Trigger. Curr Atheroscler Rep 2024; 26:289-304. [PMID: 38805145 DOI: 10.1007/s11883-024-01206-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/30/2024] [Indexed: 05/29/2024]
Abstract
PURPOSE OF REVIEW In this review, we explore the intriguing and evolving connections between bacterial extracellular membrane nanovesicles (BEMNs) and atherosclerosis development, highlighting the evidence on molecular mechanisms by which BEMNs can promote the athero-inflammatory process that is central to the progression of atherosclerosis. RECENT FINDINGS Atherosclerosis is a chronic inflammatory disease primarily driven by metabolic and lifestyle factors; however, some studies have suggested that bacterial infections may contribute to the development of both atherogenesis and inflammation in atherosclerotic lesions. In particular, the participation of BEMNs in atherosclerosis pathogenesis has attracted special attention. We provide some general insights into how the immune system responds to potential threats such as BEMNs during the development of atherosclerosis. A comprehensive understanding of contribution of BEMNs to atherosclerosis pathogenesis may lead to the development of targeted interventions for the prevention and treatment of the disease.
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Affiliation(s)
- Konstantin A Lusta
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky Russian National Center of Surgery, Moscow, 119991, Russia
| | - Volha I Summerhill
- Department of Research and Development, Institute for Atherosclerosis Research, Moscow, 121609, Russia.
| | - Victoria A Khotina
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky Russian National Center of Surgery, Moscow, 119991, Russia
| | - Vasily N Sukhorukov
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky Russian National Center of Surgery, Moscow, 119991, Russia
| | - Victor Y Glanz
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky Russian National Center of Surgery, Moscow, 119991, Russia
| | - Alexander N Orekhov
- Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Petrovsky Russian National Center of Surgery, Moscow, 119991, Russia.
- Department of Research and Development, Institute for Atherosclerosis Research, Moscow, 121609, Russia.
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Song Y, Sun M, Ma F, Xu D, Mu G, Jiao Y, Yu P, Tuo Y. Lactiplantibacillus plantarum DLPT4 Protects Against Cyclophosphamide-Induced Immunosuppression in Mice by Regulating Immune Response and Intestinal Flora. Probiotics Antimicrob Proteins 2024; 16:321-333. [PMID: 36715883 DOI: 10.1007/s12602-022-10015-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2022] [Indexed: 01/31/2023]
Abstract
In this study, the strain Lactiplantibacillus plantarum DLPT4 was investigated for the immunostimulatory activity in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice. L. plantarum DLPT4 was administered to BALB/c mice by oral gavage for 30 days, and CTX was injected intraperitoneally from the 25th to the 27th days. Intraperitoneal injection of CTX caused damage to the thymic cortex and intestines, and the immune dysfunction of the BALB/c mice. L. plantarum DLPT4 oral administration exerted immunoregulating effects evidenced by increasing serum immunoglobulin (IgA, IgG, and IgM) levels and reducing the genes expression of pro-inflammatory factors (IL-6, IL-1β, and TNF-α) of the CTX-induced immunosuppressed mice. The results of the metagenome-sequencing analysis showed that oral administration of L. plantarum DLPT4 could regulate the intestinal microbial community of the immunosuppressed mice by changing the ratio of Lactiplantibacillus and Bifidobacterium. Meanwhile, the abundance of carbohydrate enzyme (CAZyme), immune diseases metabolic pathways, and AP-1/MAPK signaling pathways were enriched in the mice administrated with L. plantarum DLPT4. In conclusion, oral administration of L. plantarum DLPT4 ameliorated symptoms of CTX-induced immunosuppressed mice by regulating gut microbiota, influencing the abundance of carbohydrate esterase in the intestinal flora, and enhancing immune metabolic activity. L. plantarum DLPT4 could be a potential probiotic to regulate the immune response.
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Affiliation(s)
- Yinglong Song
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
| | - Mengying Sun
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
| | - Fenglian Ma
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
| | - Dongxue Xu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
| | - Guangqing Mu
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China
| | - Yang Jiao
- College of Life Science and Engineering of Hexi University, Zhangye, 734000, People's Republic of China
| | - Ping Yu
- High Change (Shenyang) Child-Food Products Co, Ltd, Shenyang, 110011, People's Republic of China
| | - Yanfeng Tuo
- School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, People's Republic of China.
- Dalian Probiotics Function Research Key Laboratory, Dalian Polytechnic University, Dalian, 116034, People's Republic of China.
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Boczar KE, Shin S, deKemp RA, Dowlatshahi D, Tavoosi A, Wiefels C, Liu P, Lochnan H, MacPherson PA, Chong AY, Torres C, Leung E, Tawakol A, Ahmadi A, Garrard L, Lefebvre C, Kelly C, MacPhee P, Tilokee E, Raggi P, Wells GA, Beanlands R. The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial. BMJ Open 2023; 13:e074463. [PMID: 37949621 PMCID: PMC10649523 DOI: 10.1136/bmjopen-2023-074463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 10/06/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy. OBJECTIVE The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine's effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes. METHODS AND DESIGN CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30-120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging. DISCUSSION Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy. TRIAL REGISTRATION NUMBER NCT04181996.
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Affiliation(s)
- Kevin Emery Boczar
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Sheojung Shin
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Robert A deKemp
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Dar Dowlatshahi
- Department of Neurology, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Anahita Tavoosi
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | | | - Peter Liu
- University of Ottawa, Ottawa, Ontario, Canada
| | - Heather Lochnan
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Paul A MacPherson
- Department of Medicine, Division of Infectious Diseases, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
| | - Aun Yeong Chong
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Carlos Torres
- Department of Radiology, University of Ottawa, Ottawa, Ontario, Canada
| | - Eugene Leung
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | | | - Ali Ahmadi
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Linda Garrard
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | | | - Cathy Kelly
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Poppy MacPhee
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Everad Tilokee
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Paolo Raggi
- Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
| | - George A Wells
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
- Cardiovascular Research Methods Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada
| | - Rob Beanlands
- University of Ottawa Heart Institute, Ottawa, Ontario, Canada
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Donate-Correa J, Martín-Núñez E, Martin-Olivera A, Mora-Fernández C, Tagua VG, Ferri CM, López-Castillo Á, Delgado-Molinos A, López-Tarruella VC, Arévalo-Gómez MA, Pérez-Delgado N, González-Luis A, Navarro-González JF. Klotho inversely relates with carotid intima- media thickness in atherosclerotic patients with normal renal function (eGFR ≥60 mL/min/1.73m 2): a proof-of-concept study. Front Endocrinol (Lausanne) 2023; 14:1146012. [PMID: 37274332 PMCID: PMC10235765 DOI: 10.3389/fendo.2023.1146012] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 04/26/2023] [Indexed: 06/06/2023] Open
Abstract
INTRODUCTION Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated. METHODS We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry. RESULTS APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001). DISCUSSION The results of this study in subjects with eGFR≥60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall.
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Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
| | - Alberto Martin-Olivera
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Víctor G. Tagua
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
- Área de Medicina Preventiva y Salud Pública, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | - Carla M. Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- Escuela de Doctorado y Estudios de Posgrado, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | | | | | | | | | | | - Ainhoa González-Luis
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- Escuela de Doctorado y Estudios de Posgrado, Universidad de La Laguna, San Cristóbal de La Laguna, Spain
| | - Juan F. Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria (HUNSC), Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
- Servicio de Nefrología, HUNSC, Santa Cruz de Tenerife, Spain
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Wu K, Li Y, Lin Y, Xu B, Yang J, Mo L, Huang R, Zhang X. Structural characterization and immunomodulatory activity of an exopolysaccharide from marine-derived Aspergillus versicolor SCAU141. Int J Biol Macromol 2023; 227:329-339. [PMID: 36535356 DOI: 10.1016/j.ijbiomac.2022.12.127] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 11/27/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022]
Abstract
Until now, relatively little is known about marine-derived fungal polysaccharides and their activities. Exopolysaccharide AVP141-A was isolated from the broth of marine-derived fungus Aspergillus versicolor SCAU141 and purified by Diethylaminoethyl-Sepharose Fast Flow and Sephadex G-100. The structural characteristics of AVP141-A was studied by chemical analysis together with high-performance gel permeation chromatography, ion chromatography, Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. The results showed that AVP141-A with the molecular weight of 5.10 kDa was mainly composed of →4)-α-D-Glcp-(1→, branched by α-D-Glcp-(1→ and →6)-α-D-Glcp-(1→ at C-6 positions of the glucan backbone. In particular, sulfate ester (approximately 3.62 %) was found in AVP141-A, which was frequently considered to occur in marine-derived microbial polysaccharides rather than other microbial polysaccharides. Furthermore, AVP141-A significantly enhanced the activity of the inflammatory factors NO, COX-2 and TNF-α in RAW264.7 macrophages by activating the MAPK/p38 and NF-κB/p65 pathways. In addition, metabolomic analysis revealed that most of the pathways with significant changes in RAW264.7 macrophages treated with AVP141-A were amino acid-related pathways, and arginine was the characteristic metabolite. In conclusion, this study identified AVP141-A as a marine fungus-derived sulfated exopolysaccharide with potential for development as an immune activator.
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Affiliation(s)
- Keyue Wu
- University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Yiyang Li
- University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Yuqi Lin
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Baojun Xu
- Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University-United International College, Zhuhai 519087, China
| | - Jiajia Yang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China
| | - Li Mo
- University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China
| | - Riming Huang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
| | - Xiaoyong Zhang
- University Joint Laboratory of Guangdong Province, Hong Kong and Macao Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China.
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8
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Boczar KE, Faller E, Zeng W, Wang J, Small GR, Corrales-Medina VF, deKemp RA, Ward NC, Beanlands RSB, MacPherson P, Dwivedi G. Anti-inflammatory effect of rosuvastatin in patients with HIV infection: An FDG-PET pilot study. J Nucl Cardiol 2022; 29:3057-3068. [PMID: 34820771 DOI: 10.1007/s12350-021-02830-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/22/2021] [Indexed: 01/29/2023]
Abstract
AIMS This study aimed to evaluate markers of systemic as well as imaging markers of inflammation in the ascending aorta, bone marrow, and spleen measured by 18F-FDG PET/CT, in HIV+ patients at baseline and following therapy with rosuvastatin. METHODS AND RESULTS Of the 35 HIV+ patients enrolled, 17 were randomized to treatment with 10 mg/day rosuvastatin and 18 to usual care for 6 months. An HIV- control cohort was selected for baseline comparison of serum inflammatory markers and monocyte markers of inflammation. 18F-FDG-PET/CT imaging of bone marrow, spleen, and thoracic aorta was performed in the HIV+ cohort at baseline and 6 months. While CD14++CD16- and CCR2 expressions were reduced, serum levels of IL-7, IL-8, and MCP-1 were elevated in the HIV+ population compared to the controls. There was a significant drop in FDG uptake in the bone marrow (TBRmax), spleen (SUVmax) and thoracic aortic (TBRmax) in the statin-treated group compared to the control group (bone marrow: - 10.3 ± 16.9% versus 5.0 ± 18.9%, p = .0262; spleen: - 9.8 ± 20.3% versus 11.3 ± 28.8%, p = .0497; thoracic aorta: - 19.1 ± 24.2% versus 4.3 ± 15.4%, p = .003). CONCLUSIONS HIV+ patients had significantly markers of systemic inflammation including monocyte activation. Treatment with low-dose rosuvastatin in the HIV+ cohort significantly reduced bone marrow, spleen and thoracic aortic FDG uptake.
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Affiliation(s)
- Kevin E Boczar
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | - Elliot Faller
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Wanzhen Zeng
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Jerry Wang
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Gary R Small
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Vicente F Corrales-Medina
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Robert A deKemp
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Natalie C Ward
- School of Public Health, Curtin University, Perth, Australia
- School of Medicine, University of Western Australia, Perth, Australia
| | - Rob S B Beanlands
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Paul MacPherson
- The Ottawa Hospital Research Institute, Ottawa, ON, Canada
- Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Girish Dwivedi
- Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, ON, Canada.
- School of Medicine, University of Western Australia, Perth, Australia.
- Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, The University of Western Australia, Murdoch, Australia.
- Department of Cardiology, Fiona Stanley Hospital, Murdoch, WA, 6009, Australia.
- School of Biomedical Sciences at Curtin University, Perth, WA, Australia.
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9
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Beydoun N, Feinstein MJ. Heart Failure in Chronic Infectious and Inflammatory Conditions: Mechanistic Insights from Clinical Heterogeneity. Curr Heart Fail Rep 2022; 19:267-278. [PMID: 35838874 PMCID: PMC9283814 DOI: 10.1007/s11897-022-00560-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 01/21/2023]
Abstract
PURPOSE OF REVIEW The balance between inflammation and its resolution plays an important and increasingly appreciated role in heart failure (HF) pathogenesis. In humans, different chronic inflammatory conditions and immune-inflammatory responses to infection can lead to diverse HF manifestations. Reviewing the phenotypic and mechanistic diversity of these HF presentations offers useful clinical and scientific insights. RECENT FINDINGS HF risk is increased in patients with chronic inflammatory and autoimmune disorders and relates to disease severity. Inflammatory condition-specific HF manifestations exist and underlying pathophysiologic causes may differ across conditions. Although inflammatory disease-specific presentations of HF differ, chronic excess in inflammation and auto-inflammation relative to resolution of this inflammation is a common underlying contributor to HF. Further studies are needed to phenotypically refine inflammatory condition-specific HF pathophysiologies and prognoses, as well as potential targets for intervention.
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Affiliation(s)
- Nour Beydoun
- Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Matthew J Feinstein
- Division of Cardiology, Department of Medicine, Northwestern University, Chicago, IL, USA.
- Department of Pathology, Northwestern University, Chicago, IL, USA.
- Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
- Northwestern University Feinberg School of Medicine, 300 E. Superior St, Tarry 3-703, Chicago, IL, 60611, USA.
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10
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Shi Z, Li S, Wei Z, Wang Y, Zhou N, Ma Q, Yao Y. Immunomodulatory activity of glycoproteins isolated from chickpea (Cicer arietinum L.). Front Nutr 2022; 9:966705. [PMID: 36185682 PMCID: PMC9523481 DOI: 10.3389/fnut.2022.966705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Chickpea (Cicer arietinum L.) is a well-known legume widely used as traditional medicine. This study aimed to characterize the structure and evaluate the immunomodulatory activity of one glycoprotein [crude chickpea glycoprotein-1 (CAG-1)] isolated from chickpea. CAG-1 was extracted with hot alkaline water and purified with DEAE-Sepharose Fast Flow and Superdex-200 column chromatography. CAG-1, with a molecular weight of 8,106 Da, contained 57.12% polysaccharide and 35.41% protein. The polysaccharide part was mainly composed of glucose (Glc). The protein part was connected mainly by aspartic (Asp) and glutamic (Glu). The results of nuclear magnetic resonance (NMR) analysis indicated the presence of α-d-Glcp-(1 → 4)-α-d-Glcp-(1 → 4)-α-d-Glcp-(1 → . In addition, the sugar chains of the glycoprotein were not hydrolyzed under alkaline conditions, suggesting that the glycoprotein was N-glycosidic; thus, the sugar chain was linked to the protein chain by Asp. An immunological study showed that CAG-1 stimulated the production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein 1 (MCP-1) in RAW 264.7 macrophages in a dose-dependent manner.
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Affiliation(s)
- Zhenxing Shi
- Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
- Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing, China
- School of Food Science and Technology, Henan University of Technology, Zhengzhou, China
| | - Shiyu Li
- Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Zuchen Wei
- Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
- Laboratory for Green Cultivation and Deep Processing of Three Gorges Reservoir Area's Medicinal Herbs, College of Life Science and Engineering, Chongqing Three Gorges University, Chongqing, China
| | - Yuanji Wang
- Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Nong Zhou
- Laboratory for Green Cultivation and Deep Processing of Three Gorges Reservoir Area's Medicinal Herbs, College of Life Science and Engineering, Chongqing Three Gorges University, Chongqing, China
| | - Qiang Ma
- Department of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing, China
- *Correspondence: Qiang Ma
| | - Yang Yao
- Institute of Crop Science, Chinese Academy of Agricultural Sciences, Beijing, China
- Yang Yao
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11
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Kotlyarov S. Genetic and Epigenetic Regulation of Lipoxygenase Pathways and Reverse Cholesterol Transport in Atherogenesis. Genes (Basel) 2022; 13:1474. [PMID: 36011386 PMCID: PMC9408222 DOI: 10.3390/genes13081474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 08/12/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Atherosclerosis is one of the most important medical and social problems of modern society. Atherosclerosis causes a large number of hospitalizations, disability, and mortality. A considerable amount of evidence suggests that inflammation is one of the key links in the pathogenesis of atherosclerosis. Inflammation in the vascular wall has extensive cross-linkages with lipid metabolism, and lipid mediators act as a central link in the regulation of inflammation in the vascular wall. Data on the role of genetics and epigenetic factors in the development of atherosclerosis are of great interest. A growing body of evidence is strengthening the understanding of the significance of gene polymorphism, as well as gene expression dysregulation involved in cross-links between lipid metabolism and the innate immune system. A better understanding of the genetic basis and molecular mechanisms of disease pathogenesis is an important step towards solving the problems of its early diagnosis and treatment.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia
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12
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Wang Y, Wang Z, Tian J, Lu M. Editorial: Multimodality Imaging in Acute Coronary Syndrome. Front Cardiovasc Med 2022; 9:939428. [PMID: 35711376 PMCID: PMC9197208 DOI: 10.3389/fcvm.2022.939428] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Yining Wang
- Department of Magnetic Resonance Imaging, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhao Wang
- School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Jinwei Tian
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Minjie Lu
- Department of Magnetic Resonance Imaging, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Laboratory of Cardiovascular Imaging (Cultivation), Chinese Academy of Medical Sciences, Beijing, China
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13
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Martín-Núñez E, Pérez-Castro A, Tagua VG, Hernández-Carballo C, Ferri C, Pérez-Delgado N, Rodríguez-Ramos S, Cerro-López P, López-Castillo Á, Delgado-Molinos A, López-Tarruella VC, Arévalo-Gómez MA, González-Luis A, Martín-Olivera A, Morales-Estévez CC, Mora-Fernández C, Donate-Correa J, Navarro-González JF. Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease. Sci Rep 2022; 12:8422. [PMID: 35590090 PMCID: PMC9120199 DOI: 10.1038/s41598-022-12548-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 05/04/2022] [Indexed: 12/16/2022] Open
Abstract
Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case-control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.
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Affiliation(s)
- Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Escuela de Doctorado Y Estudios de Posgrado, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Atteneri Pérez-Castro
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Escuela de Doctorado Y Estudios de Posgrado, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Víctor G Tagua
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Instituto Universitario de Enfermedades Tropicales Y Salud Pública de Canarias, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Carolina Hernández-Carballo
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Escuela de Doctorado Y Estudios de Posgrado, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Carla Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Escuela de Doctorado Y Estudios de Posgrado, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Nayra Pérez-Delgado
- Servicio de Análisis Clínicos, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Sergio Rodríguez-Ramos
- Coordinación de Trasplantes, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Purificación Cerro-López
- Coordinación de Trasplantes, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Ángel López-Castillo
- Servicio de Cirugía Vascular, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Alejandro Delgado-Molinos
- Servicio de Cirugía Vascular, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Victoria Castro López-Tarruella
- Servicio de Anatomía Patológica, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Miguel A Arévalo-Gómez
- Departamento de Anatomía E Histología Humana, Universidad de Salamanca, 37008, Salamanca, Spain
| | - Ainhoa González-Luis
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
- Escuela de Doctorado Y Estudios de Posgrado, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain
| | - Alberto Martín-Olivera
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | | | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain
| | - Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain.
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain.
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain.
- Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, 38010, Santa Cruz de Tenerife, Tenerife, Spain.
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, 38200, San Cristóbal de La Laguna, Tenerife, Spain.
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14
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Vissenaekens H, Grootaert C, Raes K, De Munck J, Smagghe G, Boon N, Van Camp J. Quercetin Mitigates Endothelial Activation in a Novel Intestinal-Endothelial-Monocyte/Macrophage Coculture Setup. Inflammation 2022; 45:1600-1611. [PMID: 35352237 DOI: 10.1007/s10753-022-01645-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 01/16/2022] [Accepted: 02/03/2022] [Indexed: 11/30/2022]
Abstract
Atherosclerosis initiation is associated with a pro-inflammatory state of the endothelium. Quercetin is a flavonoid abundantly present in plant-based foods, with a possible impact on cardiovascular health. In this study, the effects of quercetin on lipopolysaccharide (LPS)-mediated endothelial inflammation and monocyte adhesion and migration, which are initial steps of the atherogenic process, are studied. Novel in vitro multicellular models simulating the intestinal-endothelial-monocytes/macrophages axis allowed to combine relevant intestinal flavonoid absorption, metabolism and efflux, and the consequent bioactivity towards peripheral endothelial cells. In this triple coculture, quercetin exposure decreased monocyte adhesion to and macrophage migration through an LPS-stressed endothelium, and this was associated with significantly lower levels of soluble vascular cell adhesion molecule-1 (sVCAM-1). Furthermore, quercetin decreased the pro-inflammatory cell environment upon LPS-induced endothelial activation, in terms of tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and sVCAM-1 expression. These findings highlight a mode-of-action by which quercetin may positively impact the initial states of atherosclerosis under more physiologically relevant conditions in terms of quercetin concentrations, metabolites, and intercellular crosstalk.
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Affiliation(s)
- Hanne Vissenaekens
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.,Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - Charlotte Grootaert
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Katleen Raes
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Julie De Munck
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium
| | - Guy Smagghe
- Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - Nico Boon
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
| | - John Van Camp
- Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.
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15
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Yu Q, Guo M, Zeng W, Zeng M, Zhang X, Zhang Y, Zhang W, Jiang X, Yu B. Interactions between NLRP3 inflammasome and glycolysis in macrophages: New insights into chronic inflammation pathogenesis. Immun Inflamm Dis 2022; 10:e581. [PMID: 34904398 PMCID: PMC8926505 DOI: 10.1002/iid3.581] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 11/26/2021] [Accepted: 11/30/2021] [Indexed: 12/11/2022] Open
Abstract
NLRP3 inflammasome activation in macrophages fuels sterile inflammation, which has been tied with metabolic reprogramming characterized by high glycolysis and low oxidative phosphorylation. The key enzymes in glycolysis and glycolysis‐related products can regulate and activate NLRP3 inflammasome. In turn, NLRP3 inflammasome is considered to affect glycolysis, as well. However, the exact mechanism remains ambiguous. On the basis of these findings, the focus of this review is mainly on the developments in our understanding of interaction between NLRP3 inflammasome activation and glycolysis in macrophages, and small molecule compounds that influence the activation of NLRP3 inflammasomes by regulating glycolysis in macrophages. The application of this interaction in the treatment of diseases is also discussed. This paper may yield valuable clues for development of novel therapeutic agent for NLRP3 inflammasome‐related diseases.
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Affiliation(s)
- Qun Yu
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Maojuan Guo
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wenyun Zeng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Miao Zeng
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xiaolu Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yue Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Wenlan Zhang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Xijuan Jiang
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Bin Yu
- School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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16
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Liu C, Yu Z, Chen H, Wang J, Liu W, Zhou L, Wang Y, Chen H, Zhou H, Liu Z, Han J, Jiang H, Yu L. Relationship Between Immunoinflammation and Coronary Physiology Evaluated by Quantitative Flow Ratio in Patients With Coronary Artery Disease. Front Cardiovasc Med 2021; 8:714276. [PMID: 34660716 PMCID: PMC8511462 DOI: 10.3389/fcvm.2021.714276] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 09/06/2021] [Indexed: 12/31/2022] Open
Abstract
Background: The association between coronary physiology and immunoinflammation has not been investigated. We performed a retrospective study using quantitative flow ratio (QFR) to evaluate the interaction between immunoinflammatory biomarkers and coronary physiology. Methods: A total of 172 patients with CAD who underwent coronary arteriography (CAG) and QFR were continuously enrolled from May 2020 to February 2021. As a quantitative indicator of coronary physiology, QFR can reflect the functional severity of coronary artery stenosis. The target vessel measured by QFR was defined as that with the most severe lesions. Significant coronary anatomical stenosis was defined as 70% stenosis in the target vessel. Results: Compared with the QFR > 0.8 group, interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased and CD3+ and CD4+ T lymphocyte counts were decreased in the QFR ≤ 0.8 group. In addition, patients with DS ≤ 70% had higher IL-6, IL-10, and TNF-α levels and decreased CD3+ and CD4+ T lymphocyte counts than those with DS > 70%. Logistic regression analysis indicated IL-6 to be an independent predictor of significant coronary functional and anatomic stenosis (odds ratio, 1.125; 95% CI, 1.059–1.196; P < 0.001). Receiver operating characteristic (ROC) analyses showed that IL-6 > 6.36 was predictive of QFR ≤ 0.8 of the target vessel. The combination of IL-6, IL-10 and CD4 improved the value for predicting QFR ≤ 0.8 of the target vessel (AUC, 0.737; 95% CI, 0.661–0.810). Conclusion: Among immunoinflammatory biomarkers, IL-6 was independently associated with a higher risk of QFR ≤ 0.8 of the target vessel. The combination of immunoinflammatory biomarkers was highly predictive of significant coronary functional and anatomic stenosis.
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Affiliation(s)
- Chengzhe Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zhiyao Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Huaqiang Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Jun Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Wei Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Liping Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Yueyi Wang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Hu Chen
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Huixin Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Zhihao Liu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Jiapeng Han
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Hong Jiang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
| | - Lilei Yu
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.,Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan, China.,Cardiovascular Research Institute, Wuhan University, Wuhan, China.,Hubei Key Laboratory of Cardiology, Wuhan, China
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17
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Momi S, Falcinelli E, Petito E, Ciarrocca Taranta G, Ossoli A, Gresele P. Matrix metalloproteinase-2 on activated platelets triggers endothelial PAR-1 initiating atherosclerosis. Eur Heart J 2021; 43:504-514. [PMID: 34529782 DOI: 10.1093/eurheartj/ehab631] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 04/02/2021] [Accepted: 09/09/2021] [Indexed: 11/12/2022] Open
Abstract
AIMS Platelets participate in atherogenesis with mechanisms not yet fully clarified. Vascular wall MMP-2 is involved in the arterial remodelling accompanying atherosclerosis. Platelets contain and release MMP-2 but no informations are available on its role in atherosclerotic lesion formation. METHODS AND RESULTS We generated double knockout mice lacking the LDL receptor and MMP-2 only in circulating blood cells showing that they develop significantly lesser femoral intima thickening after photochemical-induced arterial damage and atherosclerotic lesions in the aorta, measured by the en face method, after 4 months of atherogenic diet. Moreover, repeated transfusions of autologous-activated platelets in LDLR-/- mice on atherogenic diet significantly enhanced the extension of aortic atherosclerotic lesions while transfusion of activated platelets from MMP-2-/- mice did not. In vitro coincubation studies showed that platelet-derived MMP-2 plays a pivotal role in the development and progression of atherosclerosis through a complex cross-talk between activated platelets, monocyte/macrophages, and endothelial cells. Translational studies in patients with CAD and chronic HIV infection showed that platelet surface expression of MMP-2 highly significantly correlated with the degree of carotid artery stenosis. CONCLUSION We show a previously unknown mechanism of the pathway through which platelets expressing MMP-2 trigger the initial phases of atherosclerosis and provide a mechanism showing that they activate endothelial PAR-1 triggering endothelial p38MAPK signalling and the expression of adhesion molecules. The development of drugs blocking selectively platelet MMP-2 or its expression may represent a new approach to the prevention of atherosclerosis.
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Affiliation(s)
- Stefania Momi
- Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy
| | - Emanuela Falcinelli
- Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy
| | - Eleonora Petito
- Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy
| | - Giulia Ciarrocca Taranta
- Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy
| | - Alice Ossoli
- Center E. Grossi Paoletti, Department of Pharmacologic and Biomolecular Science, University of Milan, via delle Corse, Milan 06132, Italy
| | - Paolo Gresele
- Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia, Strada Vicinale Via delle Corse, Perugia 06132, Italy
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18
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Donate-Correa J, Ferri CM, Martín-Núñez E, Pérez-Delgado N, González-Luis A, Mora-Fernández C, Navarro-González JF. Klotho as a biomarker of subclinical atherosclerosis in patients with moderate to severe chronic kidney disease. Sci Rep 2021; 11:15877. [PMID: 34354161 PMCID: PMC8342510 DOI: 10.1038/s41598-021-95488-4] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 07/19/2021] [Indexed: 02/07/2023] Open
Abstract
Chronic kidney disease (CKD) has been associated with a higher risk of cardiovascular disease (CVD). CKD patients present a decrease in the levels of the protein Klotho that accompanies the decrease in kidney function. This protein has been related to protective effects against CVD. However, it is unclear whether circulating Klotho, and its expression in peripheral blood cells (PBCs) are also associated with subclinical atherosclerosis in CKD. The present study aimed to study the relationship between Klotho and subclinical atherosclerosis in a population of patients with moderate to severe CKD. We determined the serum levels and gene expression in PBCs levels of Klotho and three inflammatory cytokines in 103 patients with CKD and investigated their relationship with two surrogate markers of subclinical atherosclerotis: ankle-brachial index (ABI) and carotid intima-media thickness (CIMT). Patients with subclinical atherosclerosis presented lower serum and PBCs expression levels of Klotho. Both variables were associated with the presence of subclinical atherosclerosis, being directly related with ABI and inversely with CIMT (P < 0.0001 for both). Multiple regression analysis demonstrated that both variables were significant determinants for ABI (adjusted R2 = 0.511, P < 0.0001) and CIMT (adjusted R2 = 0.445, P < 0.0001), independently of traditional and emergent cardiovascular risk factors. Moreover, both constituted protective factors against subclinical atherosclerosis [OR: 0.993 (P = 0.002) and 0.231 (P = 0.025), respectively]. Receiver operating characteristic analysis pointed to the utility of serum Klotho (area under the curve [AUC]: 0.817, 95% CI: 0.736-0.898, P < 0.001) and its gene expression in PBCs (AUC: 0.742, 95% CI: 0.647-0.836, P < 0.001) to distinguish subclinical atherosclerosis. The reductions in serum and PBCs expression levels of Klotho in CKD patients are independently associated with the presence of for subclinical atherosclerosis. Further research exploring whether therapeutic approaches to maintain or elevate Klotho could reduce the impact of CVD in CKD patients is warranted.
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Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
| | - Carla M Ferri
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
| | - Ernesto Martín-Núñez
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
| | - Nayra Pérez-Delgado
- Clinical Analysis Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Ainhoa González-Luis
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain.
- Servicio de Nefrología, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
- REDINREN (Red de Investigación Renal-RD16/0009/0022), Instituto de Salud Carlos III, Madrid, Spain.
- Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Santa Cruz de Tenerife, Spain.
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19
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Structural analysis and biological effects of a neutral polysaccharide from the fruits of Rosa laevigata. Carbohydr Polym 2021; 265:118080. [PMID: 33966844 DOI: 10.1016/j.carbpol.2021.118080] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 04/10/2021] [Accepted: 04/11/2021] [Indexed: 02/06/2023]
Abstract
A neutral water-soluble polysaccharide (RLP50-2) was extracted and purified from the fruits of Rosa laevigata. The absolute molecular weight was determined as 1.26 × 104 g/mol. Monosaccharide composition analysis showed that RLP50-2 mainly consisted of glucose, arabinose, and galactose. Structural analysis revealed that RLP50-2 consisted of →5)-α-L-Araf-(1→, →2,5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →3,6)-β-D-Glcp-(1→, →4)-α-D-Galp-(1→, →6)-β-D-Galp-(1→, →2)-β-D-Xylp-(1→, terminal α-L-arabinose, and terminal β-D-mannose. Biological assays showed that RLP50-2 had immunomodulatory activities using cell and zebrafish models. Moreover, RLP50-2 showed significantly antitumor activities by inhibiting tumor cell proliferation and migration and blocking angiogenesis. These results suggested that RLP50-2 could be developed as a potential immunomodulatory agent or antitumor candidate drug in biomedicine field.
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20
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Zhang YM, Meng LB, Yu SJ, Ma DX. Identification of potential crucial genes in monocytes for atherosclerosis using bioinformatics analysis. J Int Med Res 2021; 48:300060520909277. [PMID: 32314637 PMCID: PMC7175059 DOI: 10.1177/0300060520909277] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Objective To use bioinformatics tools to screen for gene biomarkers from monocytes, which play an important role in the pathogenesis of atherosclerosis. Methods Two expression profiling datasets (GSE27034 and GSE10195) were obtained from the Gene Expression Omnibus dataset and the differentially expressed genes (DEGs) between atherosclerotic human peripheral blood mononuclear cells (PBMC) samples and control subjects were screened using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for the DEGs. STRING and MCODE plug-in of Cytoscape were used for constructing a protein–protein interaction network and analysing hub genes. Results The two datasets had 237 DEGs in common between non-atherosclerotic- and atherosclerotic PBMC samples. Functional annotation demonstrated that these DEGs were mainly enriched in protein binding, positive regulation of transcription from RNA polymerase II promoter, nucleus and viral carcinogenesis. Five hub genes, FBXL4, UBOX5, KBTBD6, FZR1 and FBXO2, were identified. Conclusion This present bioinformatics analysis identified that the FBXL4, UBOX5, KBTBD6 and FBXO21 genes might play vital roles in the pathogenesis of atherosclerosis. These four genes might represent new biomarkers for the diagnosis and treatment of atherosclerosis.
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Affiliation(s)
- Yuan-Meng Zhang
- Department of Internal Medicine, The Third Medical Centre of Chinese PLA General Hospital, The Training Site for Postgraduate of Jinzhou Medical University, Beijing, China
| | - Ling-Bing Meng
- Department of Neurology, Beijing Hospital, National Centre of Gerontology, Beijing, China
| | - Si-Jun Yu
- Department of Cardiology, The Third Medical Centre of Chinese PLA General Hospital, Beijing, China
| | - Dong-Xing Ma
- Department of Cardiology, The Third Medical Centre of Chinese PLA General Hospital, Beijing, China
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21
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Javadifar A, Rastgoo S, Banach M, Jamialahmadi T, Johnston TP, Sahebkar A. Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs. Int J Mol Sci 2021; 22:2529. [PMID: 33802600 PMCID: PMC7961492 DOI: 10.3390/ijms22052529] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/24/2021] [Accepted: 02/24/2021] [Indexed: 02/07/2023] Open
Abstract
Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.
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Affiliation(s)
- Amin Javadifar
- Department of Allergy and Immunology, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; (A.J.); (S.R.)
| | - Sahar Rastgoo
- Department of Allergy and Immunology, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; (A.J.); (S.R.)
| | - Maciej Banach
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, 93338 Lodz, Poland
- Polish Mother’s Memorial Hospital Research Institute (PMMHRI), 93338 Lodz, Poland
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan 9479176135, Iran;
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
| | - Thomas P. Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO 64108-2718, USA;
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948954, Iran
- Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran
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22
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Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages. Aging (Albany NY) 2021; 13:7096-7119. [PMID: 33639613 PMCID: PMC7993719 DOI: 10.18632/aging.202566] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 01/13/2021] [Indexed: 12/14/2022]
Abstract
Atherosclerosis is a chronic inflammatory disease that commonly affects the elderly and is characterized by vascular damage, macrophage infiltration, and plaque formation. Moreover, it increases the risk of cardiovascular disease. The pathogenesis of atherosclerosis involves an interplay between macrophage autophagy and apoptosis. A recently discovered transcription factor, transcription factor EB (TFEB) is known to activate autophagy in macrophages. Sirtuin deacetylase 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, activates several transcription factors, including TFEB. We studied the effects of berberine on the NAD+ synthesis pathway and interactions between SIRT1 and TFEB. We also studied the effects of berberine-induced TFEB activation via SIRT1 on autophagy and apoptosis of peritoneal macrophages. We found that berberine promoted autophagy of peritoneal macrophages by activating SIRT1 via the NAD+ synthesis pathway and, in turn, promoting TFEB nuclear translocation and deacetylation. The functional regulation of SIRT1 and TFEB by berberine could be exploited as a potential therapeutic strategy for atherosclerosis.
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23
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Ferrari D, la Sala A, Milani D, Celeghini C, Casciano F. Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development. Front Immunol 2021; 11:617804. [PMID: 33664731 PMCID: PMC7921745 DOI: 10.3389/fimmu.2020.617804] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 12/21/2020] [Indexed: 12/15/2022] Open
Abstract
Atherosclerosis is a hardening and narrowing of arteries causing a reduction of blood flow. It is a leading cause of death in industrialized countries as it causes heart attacks, strokes, and peripheral vascular disease. Pathogenesis of the atherosclerotic lesion (atheroma) relies on the accumulation of cholesterol-containing low-density lipoproteins (LDL) and on changes of artery endothelium that becomes adhesive for monocytes and lymphocytes. Immunomediated inflammatory response stimulated by lipoprotein oxidation, cytokine secretion and release of pro-inflammatory mediators, worsens the pathological context by amplifying tissue damage to the arterial lining and increasing flow-limiting stenosis. Formation of thrombi upon rupture of the endothelium and the fibrous cup may also occur, triggering thrombosis often threatening the patient’s life. Purinergic signaling, i.e., cell responses induced by stimulation of P2 and P1 membrane receptors for the extracellular nucleotides (ATP, ADP, UTP, and UDP) and nucleosides (adenosine), has been implicated in modulating the immunological response in atherosclerotic cardiovascular disease. In this review we will describe advancements in the understanding of purinergic modulation of the two main immune cells involved in atherogenesis, i.e., monocytes/macrophages and T lymphocytes, highlighting modulation of pro- and anti-atherosclerotic mediated responses of purinergic signaling in these cells and providing new insights to point out their potential clinical significance.
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Affiliation(s)
- Davide Ferrari
- Department of Life Science and Biotechnology, Section of Microbiology and Applied Pathology, University of Ferrara, Ferrara, Italy
| | - Andrea la Sala
- Certification Unit, Health Directorate, Bambino Gesù Pediatric Hospital, IRCCS, Rome, Italy
| | - Daniela Milani
- Department of Translational Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy
| | - Claudio Celeghini
- Department of Translational Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy
| | - Fabio Casciano
- Department of Translational Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy
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24
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Duraisamy P, Ravi S, Krishnan M, Livya CM, Manikandan B, Arunagirinathan K, Ramar M. Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy. Cardiovasc Hematol Agents Med Chem 2020; 20:2-12. [PMID: 33334298 DOI: 10.2174/1871525718666201217163207] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 10/20/2020] [Accepted: 10/27/2020] [Indexed: 11/22/2022]
Abstract
Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.
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Affiliation(s)
| | - Sangeetha Ravi
- Department of Zoology, University of Madras, Guindy Campus, Chennai - 600 025. India
| | - Mahalakshmi Krishnan
- Department of Zoology, University of Madras, Guindy Campus, Chennai - 600 025. India
| | - Catherene M Livya
- Department of Zoology, University of Madras, Guindy Campus, Chennai - 600 025. India
| | - Beulaja Manikandan
- Department of Biochemistry, Annai Veilankanni's College for Women, Chennai - 600 015. India
| | | | - Manikandan Ramar
- Department of Zoology, University of Madras, Guindy Campus, Chennai - 600 025. India
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25
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Gallerand A, Stunault MI, Merlin J, Guinamard RR, Yvan-Charvet L, Ivanov S. Myeloid Cell Diversity and Impact of Metabolic Cues during Atherosclerosis. IMMUNOMETABOLISM 2020; 2:immunometab20200028. [PMID: 39649554 PMCID: PMC7617020 DOI: 10.20900/immunometab20200028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/11/2024]
Abstract
Myeloid cells are key contributors to tissue, immune and metabolic homeostasis and their alteration fuels inflammation and associated disorders such as atherosclerosis. Conversely, in a classical chicken-and-egg situation, systemic and local metabolism, together with receptor-mediated activation, regulate intracellular metabolism and reprogram myeloid cell functions. Those regulatory loops are notable during the development of atherosclerotic lesions. Therefore, understanding the intricate metabolic mechanisms regulating myeloid cell biology could lead to innovative approaches to prevent and treat cardiovascular diseases. In this review, we will attempt to summarize the different metabolic factors regulating myeloid cell homeostasis and contribution to atherosclerosis, the most frequent cardiovascular disease.
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Affiliation(s)
- Alexandre Gallerand
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
| | - Marion I. Stunault
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
| | - Johanna Merlin
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
| | - Rodolphe R. Guinamard
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
| | - Laurent Yvan-Charvet
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
| | - Stoyan Ivanov
- Mediterranean center of molecular medicine (C3M)-Université Côte d’Azur–INSERM U1065, Team 13, Nice, 06200, France
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26
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Jundi D, Krayem I, Bazzi S, Karam M. In vitro effects of azide-containing human CRP isoforms and oxLDL on U937-derived macrophage production of atherosclerosis-related cytokines. Exp Ther Med 2020; 20:57. [PMID: 32952647 DOI: 10.3892/etm.2020.9185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 11/18/2019] [Indexed: 11/05/2022] Open
Abstract
Atherosclerosis is an inflammatory chronic disease of the arterial wall. Monomeric (m) and pentameric (p) C-reactive protein (CRP) and oxidized low density lipoproteins (oxLDL) seem to affect the pattern of cytokine production by macrophages, thus playing an important role in atherogenesis. Azide, the commercial preservative of CRP, may influence its action in vitro. The present study aimed to determine the effects of both isoforms of azide-containing CRP (mCRP and pCRP) with and without oxLDL on cytokine production by U937-derived macrophages. U937 monocytes were cultured and differentiated into macrophages and treated with mCRP, pCRP, oxLDL and azide individually and in combination. ELISA were performed to measure the levels of interferon-γ (IFN-γ), interleukin (IL)-4, IL-6, IL-10 and tumor necrosis factor (TNF)-α in culture supernatants collected from U937-derived macrophages following their respective treatments. Most single and combined treatments, especially in triple combination, were able to downregulate the levels of IFN-γ and IL-6 compared with control untreated cells, whilst the combination of mCRP and pCRP increased IL-4 levels. Regarding IL-10, except for an increase induced by mCRP, no significant effect was caused by any treatment compared with the control. On the other hand, the levels of TNF-α were not significantly affected by any treatment except for a decreasing trend that was observed with mCRP/oxLDL treatment compared with control. By contrast, double azide caused a significant decrease in the levels of IFN-γ and IL-6. The results of the present study indicated that mCRP, pCRP, oxLD and possibly azide, individually or in different combinations, had the tendency to upregulate the expression of IL-4 and to downregulate that of the pro-atherogenic cytokines, IFN-γ and IL-6, suggesting that the intima microenvironment serves a crucial role in atherogenesis.
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Affiliation(s)
- Dania Jundi
- Department of Biology, University of Balamand, Kourah, P. O. Box 100 Tripoli, North Governorate, Lebanon
| | - Imtissal Krayem
- Department of Biology, University of Balamand, Kourah, P. O. Box 100 Tripoli, North Governorate, Lebanon
| | - Samer Bazzi
- Department of Biology, University of Balamand, Kourah, P. O. Box 100 Tripoli, North Governorate, Lebanon
| | - Marc Karam
- Department of Biology, University of Balamand, Kourah, P. O. Box 100 Tripoli, North Governorate, Lebanon
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Effect of Interleukin-17 in the Activation of Monocyte Subsets in Patients with ST-Segment Elevation Myocardial Infarction. J Immunol Res 2020; 2020:5692829. [PMID: 32676508 PMCID: PMC7336211 DOI: 10.1155/2020/5692829] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 05/12/2020] [Accepted: 05/21/2020] [Indexed: 11/18/2022] Open
Abstract
Interleukin- (IL-) 17 is increased in acute myocardial infarction (AMI) and plays a key role in inflammatory diseases through its involvement in the activation of leukocytes. Here, we describe for the first time the effect of IL-17 in the migration and activation of monocyte subsets in patients during ST-segment elevation myocardial infarction (STEMI) and post-STEMI. We analyzed the circulating levels of IL-17 in patient plasma. A gradual increase in IL-17 was found in STEMI and post-STEMI patients. Additionally, IL-17 had a powerful effect on the recruitment of CD14++CD16+/CD14+CD16++ monocytes derived from patients post-STEMI compared with the monocytes from patients with STEMI, suggesting that IL-17 recruits monocytes with inflammatory activity post-STEMI. Furthermore, IL-17 increased the expression of TLR4 on CD14 + CD16 - and CD14++CD16+/CD14+CD16++ monocytes post-STEMI and might enhance the response to danger-associated molecular patterns post-STEMI. Moreover, IL-17 induced secretion of IL-6 from CD14++CD16- and CD14++CD16+/CD14+CD16++ monocytes both in STEMI and in post-STEMI, which indicates that IL-17 has an effect on the secretion of proinflammatory cytokines from monocytes during STEMI and post-STEMI. Overall, we demonstrate that in STEMI and post-STEMI, IL-17 is increased and induces the migration and activation of monocyte subsets, possibly contributing to the inflammatory response through TLR4 and IL-6 secretion.
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Zhang S, Li Z, Wang X, An L, Bao J, Zhang J, Cui J, Li Y, Jin DQ, Tuerhong M, Abudukeremu M, Ohizumi Y, Xu J, Guo Y. Isolation, structural elucidation, and immunoregulation properties of an arabinofuranan from the rinds of Garcinia mangostana. Carbohydr Polym 2020; 246:116567. [PMID: 32747240 DOI: 10.1016/j.carbpol.2020.116567] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 06/01/2020] [Accepted: 06/01/2020] [Indexed: 12/19/2022]
Abstract
In our search for bioactive polysaccharides as immunomodulatory agents, an arabinofuranan (GMP90-1) was purified and characterized from the rinds of Garcinia mangostana L. GMP90-1 (absolute molecular weight: 5.30 × 103 g/mol) was found to be composed of arabinose, galactose, and rhamnose. The backbone of GMP90-1 was determined as (1→5)-linked α-l-Araf, (1→2,3,5)-linked α-l-Araf, (1→3,5)-linked α-l-Araf, (1→6)-linked β-d-Galp, and (1→2)-linked α-l-Rhap. Conformational analysis revealed GMP90-1 to exist as a rigid rod structure in sodium chloride solution. To explore its potential as immunomodulatory agents, an in vitro cell screening was performed and GMP90-1 was found to significantly enhance the phagocytic uptake of neutral red and improve the secreted level of nitric oxide (NO), interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) of macrophages. Furthermore, the cellular immunomodulatory activities were confirmed by the in vivo zebrafish experiment, which suggested that GMP90-1 with immunomodulatory effects could be considered as a potential immunomodulatory for immune diseases.
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Affiliation(s)
- Shaojie Zhang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China
| | - Zhengguo Li
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China
| | - Xuelian Wang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China
| | - Lijun An
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China
| | - Jiahe Bao
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China
| | - Jie Zhang
- Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, People's Republic of China
| | - Jianlin Cui
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China
| | - Yuhao Li
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China
| | - Da-Qing Jin
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China
| | - Muhetaer Tuerhong
- College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People's Republic of China
| | - Munira Abudukeremu
- College of Chemistry and Environmental Sciences, Laboratory of Xinjiang Native Medicinal and Edible Plant Resources Chemistry, Kashgar University, Kashgar 844000, People's Republic of China
| | - Yasushi Ohizumi
- Kansei Fukushi Research Institute, Tohoku Fukushi University, Sendai 989-3201, Japan
| | - Jing Xu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People's Republic of China.
| | - Yuanqiang Guo
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Tianjin Key Laboratory of Molecular Drug Research, and Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China.
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Duncan SE, Gao S, Sarhene M, Coffie JW, Linhua D, Bao X, Jing Z, Li S, Guo R, Su J, Fan G. Macrophage Activities in Myocardial Infarction and Heart Failure. Cardiol Res Pract 2020; 2020:4375127. [PMID: 32377427 PMCID: PMC7193281 DOI: 10.1155/2020/4375127] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 01/21/2020] [Accepted: 01/27/2020] [Indexed: 02/06/2023] Open
Abstract
Heart diseases remain the major cause of death worldwide. Advances in pharmacological and biomedical management have resulted in an increasing proportion of patients surviving acute heart failure (HF). However, many survivors of HF in the early stages end up increasing the disease to chronic HF (CHF). HF is an established frequent complication of myocardial infarction (MI), and numerous influences including persistent myocardial ischemia, shocked myocardium, ventricular remodeling, infarct size, and mechanical impairments, as well as hibernating myocardium trigger the development of left ventricular systolic dysfunction following MI. Macrophage population is active in inflammatory process, yet the clear understanding of the causative roles for these macrophage cells in HF development and progression is actually incomplete. Long ago, it was thought that macrophages are of importance in the heart after MI. Also, though inflammation is as a result of adverse HF in patients, but despite the fact that broad immunosuppression therapeutic target has been used in various clinical trials, no positive results have showed up, but rather, the focus on proinflammatory cytokines has proved more benefits in patients with HF. Therefore, in this review, we discuss the recent findings and new development about macrophage activations in HF, its role in the healthy heart, and some therapeutic targets for myocardial repair. We have a strong believe that there is a need to give maximum attention to cardiac resident macrophages due to the fact that they perform various tasks in wound healing, self-renewal of the heart, and tissue remodeling. Currently, it has been discovered that the study of macrophages goes far beyond its phagocytotic roles. If researchers in future confirm that macrophages play a vital role in the heart, they can be therapeutically targeted for cardiac healing.
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Affiliation(s)
- Sophia Esi Duncan
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Shan Gao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Michael Sarhene
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Joel Wake Coffie
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Deng Linhua
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Xingru Bao
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Zhang Jing
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Sheng Li
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Rui Guo
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Jing Su
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
| | - Guanwei Fan
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
- Tianjin Laboratory of Translational Research of TCM Prescription and Syndrome, Tianjin 300193, China
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Baumer Y, Gutierrez-Huerta CA, Saxena A, Dagur PK, Langerman SD, Tamura K, Ceasar JN, Andrews MR, Mitchell V, Collins BS, Yu Q, Teague HL, Playford MP, Bleck CKE, Mehta NN, McCoy JP, Powell-Wiley TM. Immune cell phenotyping in low blood volumes for assessment of cardiovascular disease risk, development, and progression: a pilot study. J Transl Med 2020; 18:29. [PMID: 31952533 PMCID: PMC6966880 DOI: 10.1186/s12967-020-02207-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 01/02/2020] [Indexed: 12/28/2022] Open
Abstract
Background Cardiovascular disease (CVD) is the leading cause of death in the world. Given the role of immune cells in atherosclerosis development and progression, effective methods for characterizing immune cell populations are needed, particularly among populations disproportionately at risk for CVD. Results By using a variety of antibodies combined in one staining protocol, we were able to identify granulocyte, lymphocyte, and monocyte sub-populations by CD-antigen expression from 500 µl of whole blood, enabling a more extensive comparison than what is possible with a complete blood count and differential (CBC). The flow cytometry panel was established and tested in a total of 29 healthy men and women. As a proof of principle, these 29 samples were split by their race/ethnicity: African-Americans (AA) (N = 14) and Caucasians (N = 15). We found in accordance with the literature that AA had fewer granulocytes and more lymphocytes when compared to Caucasians, though the proportion of total monocytes was similar in both groups. Several new differences between AA and Caucasians were noted that had not been previously described. For example, AA had a greater proportion of platelet adhesion on non-classical monocytes when compared to Caucasians, a cell-to-cell interaction described as crucially important in CVD. We also examined our flow panel in a clinical population of AA women with known CVD risk factors (N = 20). Several of the flow cytometry parameters that cannot be measured with the CBC displayed correlations with clinical CVD risk markers. For instance, Framingham Risk Score (FRS) calculated for each participant correlated with immune cell platelet aggregates (PA) (e.g. T cell PA β = 0.59, p = 0.03 or non-classical monocyte PA β = 0.54, p = 0.02) after adjustment for body mass index (BMI). Conclusion A flow cytometry panel identified differences in granulocytes, monocytes, and lymphocytes between AA and Caucasians which may contribute to increased CVD risk in AA. Moreover, this flow panel identifies immune cell sub-populations and platelet aggregates associated with CVD risk. This flow cytometry panel may serve as an effective method for phenotyping immune cell populations involved in the development and progression of CVD.
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Affiliation(s)
- Yvonne Baumer
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Cristhian A Gutierrez-Huerta
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Ankit Saxena
- Flow Cytometry Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Pradeep K Dagur
- Flow Cytometry Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Steven D Langerman
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Kosuke Tamura
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Joniqua N Ceasar
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Marcus R Andrews
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Valerie Mitchell
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Billy S Collins
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Quan Yu
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA
| | - Heather L Teague
- Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Martin P Playford
- Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Christopher K E Bleck
- Electron Microscopy Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Nehal N Mehta
- Section of Inflammation and Cardiometabolic Diseases, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - J Philip McCoy
- Flow Cytometry Core, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Tiffany M Powell-Wiley
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Building 10-CRC, Room 5-5332, Bethesda, MD, 20892, USA. .,Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
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Zhang Y, Cartland SP, Henriquez R, Patel S, Gammelgaard B, Flouda K, Hawkins CL, Rayner BS. Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis. Redox Biol 2019; 29:101409. [PMID: 31926617 PMCID: PMC6928357 DOI: 10.1016/j.redox.2019.101409] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Accepted: 12/11/2019] [Indexed: 12/21/2022] Open
Abstract
Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE−/-) mouse model of atherosclerosis. Dietary supplementation with SeMet (2 mg/kg) increased the tissue concentration of Se, and the expression and activity of glutathione peroxidase, compared to non-supplemented controls. Supplementation with SeMet significantly reduced atherosclerotic plaque formation in mouse aortae, resulted in a more stable lesion phenotype and improved vessel function. Concurrent with these results, SeMet supplementation decreased lesion accumulation of M1 inflammatory type macrophages, and decreased the extent of extracellular trap release from phorbol myristate acetate (PMA)-stimulated mouse bone marrow-derived cells. Importantly, these latter results were replicated within ex-vivo experiments on cultured neutrophils isolated from acute coronary syndrome patients, indicating the ability of SeMet to alter the acute inflammatory response within a clinically-relevant setting. Together, these data highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.
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Affiliation(s)
- Yunjia Zhang
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia
| | - Siân P Cartland
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia
| | - Rodney Henriquez
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia
| | - Sanjay Patel
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW, 2050, Australia
| | - Bente Gammelgaard
- Department of Pharmacy, University of Copenhagen, Universitetsparken 2, Copenhagen, DK-2100, Denmark
| | - Konstantina Flouda
- Department of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3, Copenhagen, DK-2200, Denmark
| | - Clare L Hawkins
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia; Department of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3, Copenhagen, DK-2200, Denmark
| | - Benjamin S Rayner
- Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW, 2042, Australia; Sydney Medical School, Edward Ford Building A27, University of Sydney, Sydney, NSW, 2006, Australia.
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Immunomodulatory effect of natural flavonoid chrysin (5, 7-dihydroxyflavone) on LPS stimulated RAW 264.7 macrophages via inhibition of NF-κB activation. Process Biochem 2019. [DOI: 10.1016/j.procbio.2019.05.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Duan Y, Zhang Y, Qu C, Yu W, Tana, Shen C. CKLF1 aggravates neointimal hyperplasia by inhibiting apoptosis of vascular smooth muscle cells through PI3K/AKT/NF-κB signaling. Biomed Pharmacother 2019; 117:108986. [PMID: 31387172 DOI: 10.1016/j.biopha.2019.108986] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 05/08/2019] [Accepted: 05/13/2019] [Indexed: 12/20/2022] Open
Abstract
Chemokine-like factor 1 (CKLF1) is a cytokine, which has a detrimental effect on the multiple disease progression. Our previous studies reported that arterial injury induced the upregulation of CKLF1 expression in artery at 7-14 days after injury. Here, using a rat carotid balloon injury model, we found that CKLF1 knockdown in the injured site abolished neointimal formation and even decreased medial area; contrarily, CKLF1 overexpression developed a thicker neointima than controls, demonstrating that CKLF1 exerted positive effects on neointimal hyperplasia and the accumulation of vascular smooth muscle cells (VSMC). The mechanism study indicated that CKLF1 reduced susceptibility to the cell cycle G2/M arrest and apoptosis, and thereby speeding up VSMC accumulation. This role of CKLF1 was tightly associated with phosphatidylinositol (PI) 3-kinase signaling pathway. CKLF1 increased the expression of four isoforms of the PI3-kinase catalytic subunits, which in turn activated its downstream targets Akt and an effector NF-κB accepted as critical transcription factors of cell survival and proliferation. Furthermore, RNA-sequencing analysis revealed that CKLF1 had wide-ranging roles in regulating the expression of genes that mainly engaged in cell apoptosis and innate immune response. Collectively, the data allow us to conclude that high level CKLF1 after artery injury switches the balance of VSMC proliferation and apoptosis through PI3K/AKT/NF-κB signaling and consequently leads to neointimal hyperplasia. The findings shed insight into new treatment strategies to limit restenosis based on CKLF1 as a future target.
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Affiliation(s)
- Yanyu Duan
- Department of Vascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou 341000, China
| | - Yongbao Zhang
- Department of Vascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Chengjia Qu
- Department of Vascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
| | - Weidong Yu
- Department of Central Laboratory, Peking University People's Hospital, Beijing 100044, China
| | - Tana
- Department of Central Laboratory, Peking University People's Hospital, Beijing 100044, China
| | - Chenyang Shen
- Department of Vascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
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Zhang YG, Song Y, Guo XL, Miao RY, Fu YQ, Miao CF, Zhang C. Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis. Cell Cycle 2019; 18:2674-2684. [PMID: 31416388 DOI: 10.1080/15384101.2019.1654797] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
This study aimed to investigate the role and underlying mechanism of exosomes secreted by oxidized low-density lipoprotein (oxLDL)-stimulated macrophages in the progression of atherosclerosis (AS). Exosomes from peripheral blood of AS patients or oxLDL-treated macrophages were co-cultured with human neutrophils. Neutrophil extracellular traps (NETs) were detected by immunofluorescence staining. The levels of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-146a and superoxide dismutase 2 (SOD2) were determined by quantitative real-time PCR (qRT-PCR) and western blot. The generation of intracellular reactive oxygen species (ROS) was observed by using dichlorofluorescin diacetate (DCFH-DA). ApoE-deficient mice were fed with high-fat diet (HFD) to induce AS. Atherosclerotic plaques were evaluated by Oil red O (ORO) and hematoxylin-eosin (HE) staining. Our results showed that miRNA-146a was enriched in serum-derived exosomes of AS patients and oxLDL-treated macrophage THP-1-derived exosomes. Importantly, exosomal miR-146a secreted by oxLDL-treated macrophages promoted ROS and NETs release via targeting SOD2. In addition, intravenous administration of oxLDL-treated THP-1 cells-derived exosomes into AS mice significantly deteriorated AS in vivo. Our findings indicate that exosomal miR-146a derived from oxLDL-treated macrophages promotes NETs formation via inducing oxidative stress, which might provide a novel scientific basis for the understanding of AS progression.
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Affiliation(s)
- Yong-Gan Zhang
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Yan Song
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Xue-Li Guo
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Ren-Ying Miao
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Yi-Qun Fu
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Chao-Feng Miao
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
| | - Chuang Zhang
- Department of Vascular Surgery, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China
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Suraiya S, Jang WJ, Cho HJ, Choi YB, Park HD, Kim JM, Kong IS. Immunomodulatory Effects of Monascus spp.-Fermented Sacccharina japonica Extracts on the Cytokine Gene Expression of THP-1 Cells. Appl Biochem Biotechnol 2019; 188:498-513. [PMID: 30536032 DOI: 10.1007/s12010-018-02930-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Accepted: 11/30/2018] [Indexed: 12/21/2022]
Abstract
The immunomodulatory effects of Monascus-fermented Saccharina japonica extract on anti- and pro-inflammatory cytokines gene expression of THP-1 cells were evaluated. Extracts of fermented samples showed higher phenolic, flavonoid, protein, and reducing sugar contents than unfermented one. Fermented samples were rich in many bioactive compounds determined by GC-MS analyses and showed cell viability greater than 85% in MTS assay. Regarding the anti-inflammatory and pro-inflammatory activities of the different samples, Q-PCR analyses revealed that IL-10 gene expression in THP-1 cells was significantly higher (p < 0.05) in cells treated with the SjMp or SjMk sample than those treated with the unfermented sample. Cells treated with the SjMp extract or lipopolysaccharide (LPS) showed significantly (p < 0.05) higher relative gene expression of IL-4 cytokine than cells treated with SjMk or SjU extracts. The relative gene expression of IFN-α was higher in cells treated with SjMp followed by LPS, SjMk, and SjU. TGF-β expression was higher in LPS-stimulated cells followed by SjMk and other samples. Cells treated with SjMp exhibited significantly higher pro-inflammatory (IL-6, IL-8, TNF-α, and NF-κB) cytokine gene expression than cells treated with SjU. These results revealed that extracts from S. japonica fermented with Monascus spp. regulate cytokine gene expression. Graphical abstract ᅟ.
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Affiliation(s)
- Sharmin Suraiya
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
- Department of Fisheries and Marine Bioscience, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, 8100, Bangladesh
| | - Won Je Jang
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
| | - Hwa Jin Cho
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
| | - Yu Bin Choi
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
| | - Hae Dae Park
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea
| | - Jin-Man Kim
- Department of Biotechnology, Chonnam National University, 50, Daehak-ro, Yeosu, 59626, Republic of Korea
| | - In-Soo Kong
- Department of Biotechnology, College of Fisheries Science, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan, 48513, Republic of Korea.
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Liu JX, Li X, Ji WJ, Yan LF, Li T, Li YX, Xu ZW, Yang GH, Li YM, Zhao JH, Zhou X. The Dynamics of Circulating Monocyte Subsets and Intra-Plaque Proliferating Macrophages during the Development of Atherosclerosis in ApoE -/- Mice. Int Heart J 2019; 60:746-755. [PMID: 31019169 DOI: 10.1536/ihj.17-681] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
To detect the development of monocytes and proliferative macrophages in atherosclerosis of ApoE-/- mice, we randomly assigned 84 ApoE-/- mice fed western diet or chow diet. On weeks 2, 4, 6, 8, 10, and 12 after fed high-fat diet or normal chow diet, animals were euthanized (n = 7 for each group at each time point). Flow cytometry methods were used to analyze the proportions of circulation monocyte subsets. The macrophage and proliferative macrophage accumulation within atherosclerotic plaques was estimated by confocal florescence microscopy. Plasma levels of total cholesterol and triglyceride were measured by ELISA kit. The plaques of aortic sinus were stained with Oil Red O. The percent of Ly6Chi circulation monocyte, the density of proliferation macrophage, the total plasma cholesterol and triglyceride levels, the lesion area of ApoE-/- mice were consistently elevated in chow diet throughout the trial. The total plasma cholesterol and triglyceride levels, the lesion area were elevated in western diet group with age, and they were always higher than the chow diet group. The Ly6Chi monocytes and proliferative macrophages reached a plateau at 8 weeks and 6 weeks; despite continued high-triglyceride high-cholesterol diet the percent did not significantly change. Interestingly, the density of macrophage did not change significantly over age in western and chow diet groups. Our results provide a dynamic view of Ly6Chi monocyte subset, the density of macrophage and proliferation macrophage change during the development and progression of atherosclerosis, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.
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Affiliation(s)
- Jun-Xiang Liu
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | | | - Wen-Jie Ji
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Li-Fang Yan
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Tan Li
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Yu-Xiu Li
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Zhong-Wei Xu
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Guo-Hong Yang
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Yu-Ming Li
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Ji-Hong Zhao
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
| | - Xin Zhou
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Logistics University of PAPF
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Zhang M, Zheng Y, Sun Y, Li S, Chen L, Jin X, Hou X, Liu X, Chen Q, Li J, Liu M, Zheng X, Zhang Y, Wu J, Yu B. Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome. Am J Cancer Res 2019; 9:3425-3442. [PMID: 31281488 PMCID: PMC6587165 DOI: 10.7150/thno.33178] [Citation(s) in RCA: 92] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Accepted: 04/29/2019] [Indexed: 12/12/2022] Open
Abstract
Rationale: Tolerogenic dendritic cells (tol-DCs) play essential roles in immune-related diseases and induce immune tolerance by shaping T-cell responses. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in the immune system. However, the potential roles and underlying mechanisms of lncRNAs in tol-DCs remain unclear. Methods: RNA in-situ hybridization, histochemistry, and qRT-PCR were performed to determine the distribution and expression of NEAT1 in DCs. Flow cytometry was used to analyze the tolerogenic function of DCs. Small sequencing, followed by bioinformatic analysis, was performed to determine the target genes of NEAT1. The mechanism of NEAT1 was explored using a luciferase reporter, chromatin immunoprecipitation assays, and Immunofluorescence. In-vivo experiments were used to investigate the induction of immune tolerance via NEAT1-knockdown DCs. Results: Our results show that lncRNA NEAT1 can induce tolerogenic phenotype in DCs. Mechanistically, small RNA-seq analysis revealed that NEAT1 knockdown preferentially affected the expression of miR-3076-3p. Furthermore, NEAT1 used the NLRP3 inflammasome as a molecular decoy for miR-3076-3p, thus facilitating the expression of tolerogenic phenotype in DCs. Moreover, the transcription factor E2F1 acted as a repressor of NEAT1 transcription via activity of H3K27ac. Our results also indicate that NEAT1 knockdown in DCs can induce immune tolerance in models of experimental autoimmune myocarditis and heart transplantation. Conclusions: Taken together, our study shows the mechanism used by NEAT1 in inducing tol-DCs and highlights the therapeutic potential of targeting NEAT1 for the treatment of immune-related diseases.
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Huang Z, Liu Y, Liang L, Liu W, Sooranna SR, Mo J, Liu L, Li Z, Guo J. Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China. Gene 2019; 708:1-9. [PMID: 31082501 DOI: 10.1016/j.gene.2019.05.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Revised: 04/14/2019] [Accepted: 05/06/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Toll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. METHODS 1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. RESULTS There are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. CONCLUSIONS The rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.
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Affiliation(s)
- Zhaohe Huang
- Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou 510630, People's Republic of China; Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Yan Liu
- Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou 510630, People's Republic of China; Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Limei Liang
- Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Wenjing Liu
- Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Suren R Sooranna
- Department of Surgery and Cancer, Imperial College London, Chelsea and Westminster Hospital, 369, Fulham Road, London SW10 9NH, UK.
| | - Jianjiao Mo
- Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Li Liu
- Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Zhile Li
- Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China
| | - Jun Guo
- Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou 510630, People's Republic of China.
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Ferronato S, Scuro A, Fochi S, Orlandi E, Gomez-Lira M, Olivato S, Mazzucco S, Turco A, Romanelli MG. Expression of TLR4-PTGE2 signaling genes in atherosclerotic carotid plaques and peripheral blood. Mol Biol Rep 2018; 46:1317-1321. [PMID: 30421129 DOI: 10.1007/s11033-018-4478-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Accepted: 11/07/2018] [Indexed: 01/01/2023]
Abstract
Toll-like receptor 4 (TLR4)/prostaglandine synthetase 2 (PTGS2) signaling plays a relevant role in atherosclerotic plaque vulnerability. The purpose of this study was to check the gene expression of 6 genes participating to TLR4/PTGS2 signaling (TLR4, PTGS2, ACSL4, PTGER3, PTGER4, and EPRAP) in carotid plaques and blood samples from the same individual and to evaluate these genes as biomarker of plaque progression. We investigated differential gene expression by qRT-PCR in 62 atherosclerotic patients' carotid plaques and corresponding blood sample. A very weak or no correlation was observed in the overall population or analyzing asymptomatic patients. These analyzed genes are most likely not suitable for inclusion in the clinical routine as biomarkers of plaque instability.
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Affiliation(s)
- S Ferronato
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy
| | - A Scuro
- Department of Surgery, Dentistry, Pediatrics and Gynaecology, Unit of Vascular and Endovascular Surgery, University of Verona, Verona, Italy
| | - S Fochi
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy
| | - E Orlandi
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy
| | - M Gomez-Lira
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy.
| | - S Olivato
- Section of Neurophatology, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Verona, Italy
| | - S Mazzucco
- Department of Clinical Neurosciences, Centre for Prevention of Stroke and Dementia Nuffield, University of Oxford, Oxford, UK
| | - A Turco
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy
| | - M G Romanelli
- Section of Biology and Genetics, Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134, Verona, Italy
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40
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Hu S, Zhu L. Semaphorins and Their Receptors: From Axonal Guidance to Atherosclerosis. Front Physiol 2018; 9:1236. [PMID: 30405423 PMCID: PMC6196129 DOI: 10.3389/fphys.2018.01236] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Accepted: 08/15/2018] [Indexed: 12/24/2022] Open
Abstract
Semaphorins are a large family of secreted, transmembrane, or GPI-anchored proteins initially identified as axon guidance cues signaling through their receptors, neuropilins, and plexins. Emerging evidence suggests that beyond the guidance, they also function in a broad spectrum of pathophysiological conditions, including atherosclerosis, a vascular inflammatory disease. Particular semaphorin members have been demonstrated to participate in atherosclerosis via eliciting endothelial dysfunction, leukocyte infiltration, monocyte-macrophage retention, platelet hyperreactivity, and neovascularization. In this review, we focus on the role of those semaphorin family members in the development of atherosclerosis and highlight the mechanistic relevance of semaphorins to atherogenesis.
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Affiliation(s)
- Shuhong Hu
- Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Li Zhu
- Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
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41
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Genre F, Rueda-Gotor J, Remuzgo-Martínez S, Corrales A, Mijares V, Expósito R, Mata C, Portilla V, Blanco R, Hernández JL, Llorca J, Gualillo O, López-Mejías R, González-Gay MA. Association of circulating calprotectin with lipid profile in axial spondyloarthritis. Sci Rep 2018; 8:13728. [PMID: 30213986 PMCID: PMC6137145 DOI: 10.1038/s41598-018-32199-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 09/04/2018] [Indexed: 02/07/2023] Open
Abstract
Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3 mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.
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Affiliation(s)
- Fernanda Genre
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Javier Rueda-Gotor
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Sara Remuzgo-Martínez
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Alfonso Corrales
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Verónica Mijares
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Rosa Expósito
- Division of Rheumatology, Hospital Comarcal de Laredo, Laredo, 39770, Spain
| | - Cristina Mata
- Division of Rheumatology, Hospital Comarcal de Laredo, Laredo, 39770, Spain
| | - Virginia Portilla
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - Ricardo Blanco
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain
| | - José Luis Hernández
- Bone Metabolism Unit, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla, IDIVAL, University of Cantabria, RETICEF, Santander, 39008, Spain
| | - Javier Llorca
- Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, 39011, Spain
| | - Oreste Gualillo
- SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), The NEIRID Group (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Santiago University Clinical Hospital, Santiago de Compostela, 15706, Spain
| | - Raquel López-Mejías
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain.
| | - Miguel A González-Gay
- Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, IDIVAL, Santander, 39011, Spain. .,School of Medicine, University of Cantabria, Santander, 39011, Spain. .,Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa.
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Bahrami A, Parsamanesh N, Atkin SL, Banach M, Sahebkar A. Effect of statins on toll-like receptors: a new insight to pleiotropic effects. Pharmacol Res 2018; 135:230-238. [PMID: 30120976 DOI: 10.1016/j.phrs.2018.08.014] [Citation(s) in RCA: 134] [Impact Index Per Article: 19.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/13/2018] [Indexed: 12/27/2022]
Abstract
The toll-like receptors (TLRs) are a class of transmembrane-spanning receptors that are sentinels of both innate and adaptive immunity. Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are the most commonly prescribed therapeutic agents for treating hypercholesterolemia globally. However, statin therapy appears to have pleiotropic effects including attenuation of chronic low-grade inflammation and modulation of TLR activity. Statins through abolition of TLR4 expression and regulation of the TLR4/Myd88/NF-κB signaling pathway may slow the progression of atherosclerosis and other inflammatory diseases. In this review, we have focused on the impact and mechanism of action of statins on cardiovascular and non-cardiovascular diseases.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Negin Parsamanesh
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | | | - Maciej Banach
- Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Amirhossein Sahebkar
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Ayoub KF, Pothineni NVK, Rutland J, Ding Z, Mehta JL. Immunity, Inflammation, and Oxidative Stress in Heart Failure: Emerging Molecular Targets. Cardiovasc Drugs Ther 2018; 31:593-608. [PMID: 28956198 DOI: 10.1007/s10557-017-6752-z] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
PURPOSE Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Although various therapies developed over the last two decades have shown improved long term outcomes in patients with established HF, there has been little progress in preventing the adverse cardiac remodeling that initiates HF. To fill the gap in treatment, current research efforts are focused on understanding novel mechanisms and signaling pathways. Immune activation, inflammation, oxidative stress, alterations in mitochondrial bioenergetics, and autophagy have been postulated as important pathophysiological events in this process. An improved understanding of these complex processes could facilitate a therapeutic shift toward molecular targets that can potentially alter the course of HF. METHODS In this review, we address the role of immunity, inflammation, and oxidative stress as well as other novel emerging concepts in the pathophysiology of HF that may have therapeutic implications. CONCLUSION Based on the experimental and clinical studies presented here, we anticipate that a better understanding of the pathophysiology of HF will open the door for new therapeutic targets. A one-size-fits-all approach may not be appropriate for all patients with HF, and further clinical trials utilizing molecular targeting in HF may result in improved outcomes.
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Affiliation(s)
- Karam F Ayoub
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Naga Venkata K Pothineni
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Joshua Rutland
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Zufeng Ding
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Jawahar L Mehta
- Division of Cardiology, Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA. .,Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham Street, #532, Little Rock, AR, 72205, USA.
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Zha Z, Wang SY, Chu W, Lv Y, Kan H, Chen Q, Zhong L, Yue L, Xiao J, Wang Y, Yin H. Isolation, purification, structural characterization and immunostimulatory activity of water-soluble polysaccharides from Lepidium meyenii. PHYTOCHEMISTRY 2018; 147:184-193. [PMID: 29353155 DOI: 10.1016/j.phytochem.2018.01.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2017] [Revised: 01/05/2018] [Accepted: 01/07/2018] [Indexed: 06/07/2023]
Abstract
A water-soluble polysaccharide LMP-1 was isolated and purified by ion-exchange chromatography from maca (Lepidium meyenii Walp.). LMP-1 has a molecular weight of 1.01 × 104 Da, and is composed of glucose and arabinose with a molar ratio of 7.03:1.08. Methylation and the 1D and 2D NMR spectroscopy of LMP-1 revealed that it is mainly composed of →4)-α-D-Glcp-(1→, →6)-α-D-Glcp-(1→, →3)-α-D-Glcp-(1→, and β-D-Araf-(1→, with branching at O-6 of →4,6)-α-D-Glcp-(1 → . LMP-1 showed up-regulation of Toll-like receptor 4 (TLR4) and Toll-like receptor 2 (TLR2). The upstream proteins of Toll-like receptors (TLRs) (CD14 and MD2) and mRNA level of IL-1β also increased. Increased transcription factor nuclear factor-kappa B (NF-κB) p65 was found in the nuclei and cytoplasm in LMP-1-treated RAW264.7 macrophages. These results indicated that LMP-1 activated RAW264.7 macrophages and elicited immunostimulatory activities via the TLRs/NF-κB signalling pathway.
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Affiliation(s)
- Zhengqi Zha
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Su-Yan Wang
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Weihua Chu
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Yang Lv
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Hongjin Kan
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Qiuli Chen
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, People's Republic of China
| | - Lili Zhong
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Long Yue
- School of Engineering, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Jinna Xiao
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China
| | - Ying Wang
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
| | - Hongping Yin
- School of Life Science and Technology, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
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Zhang TT, Zheng CY, Hu T, Jiang JG, Zhao JW, Zhu W. Polyphenols from Ilex latifolia Thunb. (a Chinese bitter tea) exert anti-atherosclerotic activity through suppressing NF-κB activation and phosphorylation of ERK1/2 in macrophages. MEDCHEMCOMM 2018; 9:254-263. [PMID: 30108919 PMCID: PMC6083792 DOI: 10.1039/c7md00477j] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 12/05/2017] [Indexed: 11/21/2022]
Abstract
Ilex latifolia Thunb is a kind of herbal tea and widely consumed as a functional tea beverage in Asian countries. In this study, polyphenols were extracted from I. latifolia and the major compounds were identified by liquid chromatography-mass spectrometry (LC-MS), then the effect on oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation was investigated. Results showed that the polyphenols could significantly inhibit ox-LDL-induced macrophage foam cell formation and suppress lipid droplet accumulation and cholesterol uptake in RAW 264.7 cells. Additionally, the secretion of pro-inflammatory cytokines, such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS), was significantly inhibited. Moreover, the polyphenols could suppress the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and clusters of differentiation 36 (CD 36), which were receptors for ox-LDL. Mechanistically, I. latifolia polyphenols could inhibit macrophage foam cell formation by suppressing NF-κB activation and phosphorylation of ERK1/2.
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Affiliation(s)
- Tian-Tian Zhang
- Department of Food Science and Technology , South China University of Technology , Guangzhou , 510640 , China . ; ; Tel: +8620 87113849
- College of Food Science and Engineering , Ocean University of China , Qingdao 266003 , China
| | - Chao-Yang Zheng
- The Second Institute of Clinical Medicine , Guangzhou University of Chinese Medicine , Guangzhou 510120 , China . ; ; Tel: +86 20 39318571
| | - Ting Hu
- Department of Food Science and Technology , South China University of Technology , Guangzhou , 510640 , China . ; ; Tel: +8620 87113849
| | - Jian-Guo Jiang
- Department of Food Science and Technology , South China University of Technology , Guangzhou , 510640 , China . ; ; Tel: +8620 87113849
| | - Jing-Wen Zhao
- The Second Institute of Clinical Medicine , Guangzhou University of Chinese Medicine , Guangzhou 510120 , China . ; ; Tel: +86 20 39318571
| | - Wei Zhu
- The Second Institute of Clinical Medicine , Guangzhou University of Chinese Medicine , Guangzhou 510120 , China . ; ; Tel: +86 20 39318571
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Zanchet B, Gomes DB, Corralo VS, Diel KA, Schönell AP, Faust C, Nicola P, Muller LG, Zanatta AP, Wildner SM, Bevilaqua F, Chitolina R, Sachett A, Zanatta L, Duarte MM, Conterato GM, Rocha CQ, Peretti C, Brumelhaus T, Alves NS, Menegatt JC, Conte F, Serena G, Ramos AT, Zimermann FC, Junior WAR. Effects of hydroalcoholic extract of Celtis iguanaea on markers of cardiovascular diseases and glucose metabolism in cholesterol-fed rats. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY 2018. [DOI: 10.1016/j.bjp.2017.12.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Zhang N, Zhang M, Liu RT, Zhang P, Yang CL, Yue LT, Li H, Li YK, Duan RS. Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis. Eur J Pharmacol 2017; 821:49-56. [PMID: 29288118 DOI: 10.1016/j.ejphar.2017.12.050] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 12/20/2017] [Accepted: 12/21/2017] [Indexed: 12/20/2022]
Abstract
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control. Both statins treatment reduced the expressions of Tim-3 on NK cells and their subtypes, natural killer T (NKT) cells and CD3+ T cells, and increased the proportions of NKT cells among peripheral blood mononuclear cells, accompanied by the decreased levels of total cholesterol, low density lipoprotein, and increased ratios of high density lipoprotein to cholesterol. These may contribute to the functions of statins in the treatment of atherosclerosis.
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Affiliation(s)
- Na Zhang
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Min Zhang
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Ru-Tao Liu
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Peng Zhang
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Chun-Lin Yang
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Long-Tao Yue
- Central laboratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Heng Li
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Yong-Kang Li
- Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
| | - Rui-Sheng Duan
- Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China.
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Affiliation(s)
- Mark M. Hughes
- School of Biochemistry and Immunology; Trinity Biomedical Sciences Institute; Trinity College Dublin; Dublin Ireland
| | - Luke A.J. O'Neill
- School of Biochemistry and Immunology; Trinity Biomedical Sciences Institute; Trinity College Dublin; Dublin Ireland
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Gonzalez L, Qian AS, Tahir U, Yu P, Trigatti BL. Sphingosine-1-Phosphate Receptor 1, Expressed in Myeloid Cells, Slows Diet-Induced Atherosclerosis and Protects against Macrophage Apoptosis in Ldlr KO Mice. Int J Mol Sci 2017; 18:ijms18122721. [PMID: 29244772 PMCID: PMC5751322 DOI: 10.3390/ijms18122721] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 12/08/2017] [Accepted: 12/08/2017] [Indexed: 12/25/2022] Open
Abstract
We generated myeloid specific sphingosine-1-phosphate receptor 1 (S1pr1) deficient mice by crossing mice that had myeloid specific expression of Cre recombinase (lyzMCre) with mice having the S1pr1 gene flanked by loxP recombination sites. We transplanted bone marrow from these mice and control lyzMCre mice with intact macrophage S1pr1 gene expression into low-density lipoprotein (LDL) receptor gene (Ldlr) deficient mice. The resulting chimeras were fed a high fat atherogenic diet for nine or twelve weeks and evaluated for atherosclerosis development in the aortic sinus. Selective S1pr1 deficiency in bone marrow-derived myeloid cells resulted in accelerated development of atherosclerosis, necrotic core formation and the appearance of apoptotic cells within atherosclerotic plaques of Ldlr knockout mice in response to a high fat diet. Examination of macrophages in culture revealed that the sphingosine-1-phosphate receptor 1 selective agonist, SEW2871 or high density lipoprotein (HDL), protected macrophages against apoptosis induced by endoplasmic reticulum (ER) stress or oxidized LDL, through activation of phosphatidylinositol-3-kinase/Akt signaling. Targeted S1pr1-deletion prevented Akt activation and protection against apoptosis by either SEW2871 or HDL. Our data suggests that sphingosine-1-phosphate receptor 1 in macrophages plays an important role in protecting them against apoptosis in vitro and in atherosclerotic plaques in vivo, and delays diet induced atherosclerosis development in Ldlr deficient mice.
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Affiliation(s)
- Leticia Gonzalez
- Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
| | - Alexander S Qian
- Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
| | - Usama Tahir
- Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
| | - Pei Yu
- Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
| | - Bernardo L Trigatti
- Department of Biochemistry and Biomedical Sciences, and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON L8L 2X2, Canada.
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50
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Blanco-Favela F, Espinosa-Luna JE, Chávez-Rueda AK, Madrid-Miller A, Chávez-Sánchez L. Effect of Native and Minimally Modified Low-density Lipoprotein on the Activation of Monocyte Subsets. Arch Med Res 2017; 48:432-440. [PMID: 29133194 DOI: 10.1016/j.arcmed.2017.11.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2016] [Accepted: 11/02/2017] [Indexed: 01/16/2023]
Abstract
BACKGROUND In atherosclerosis, monocytes are essential and secrete pro-inflammatory cytokines in response to modified low-density lipoprotein (LDL). Human CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes produce different cytokines. The objective of this research was to determine the number of monocyte subsets positives to cytokines in response to native (nLDL) and minimally modified LDL (mmLDL). METHODS Human monocytes from healthy individuals were purified by negative selection and were stimulated with nLDL, mmLDL or LPS. Subsequently, human total monocytes were incubated with monoclonal antibodies specific for CD14 or both CD14 and CD16 to characterize total monocytes and monocyte subsets and with antibodies specific to anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-6 and anti-IL-10. The number of cells positive for cytokines was determined and cells cultured with nLDL, mmLDL and LPS were compared with cells cultured only with culture medium. RESULTS We found that nLDL does not induce in the total monocyte population or in the three monocyte subsets positives to cytokines. MmLDL induced in total monocytes positives to TNF-α and IL-6 as well as in both CD14++CD16+ and CD14+CD16++ and in CD14++CD16+ monocytes, respectively. Moreover, total monocytes and the three monocyte subsets expressed few amounts of cells positives to IL-10 in response to mmLDL. CONCLUSION Our study demonstrated that nLDL did not induce cells positives to cytokines and that the CD14++CD16+ and CD14+CD16++ monocyte subsets could be the main sources of TNF-α and IL-6, respectively, in response to mmLDL, which promotes the development and progression of atherosclerotic plaque.
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Affiliation(s)
- Francisco Blanco-Favela
- Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - José Esteban Espinosa-Luna
- Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Adriana Karina Chávez-Rueda
- Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Alejandra Madrid-Miller
- Coordinación de Educación en Salud, Instituto Mexicano del Seguro Social, Ciudad de México, México
| | - Luis Chávez-Sánchez
- Unidad de Investigación Médica en Inmunología, Unidad Médica de Alta Especialidad, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México.
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