|
1
|
Glogowska E, Jose GP, Dias Araújo AR, Arhatte M, Divita R, Borowczyk C, Barouillet T, Wang B, Brau F, Peyronnet R, Patel A, Mesmin B, Harayama T, Antonny B, Xu A, Yvan-Charvet L, Honoré E. Potentiation of macrophage Piezo1 by atherogenic 7-ketocholesterol. Cell Rep 2025; 44:115542. [PMID: 40215166 DOI: 10.1016/j.celrep.2025.115542] [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: 10/24/2024] [Revised: 03/13/2025] [Accepted: 03/19/2025] [Indexed: 04/26/2025] Open
Abstract
The mechanosensitive ion channel Piezo1 present in endothelial and smooth muscle cells, as well as in macrophages, is emerging as a novel, important player in the etiology of atherosclerosis. Here, we show that myeloid-specific deficiency of Piezo1 in atherogenic Ldlr-/- mice reduces plaque formation. Moreover, chronic oxLDL, as well as its main oxysterol 7-ketocholesterol (7-KC), promotes Piezo1 opening by pressure stimulation in both mouse macrophages and transfected HEK cells. 7-KC dramatically enhances Piezo1 current amplitude and slows down inactivation and deactivation. This up-modulation involves an increase in Piezo1 expression, as well as a potentiation of mechanical gating that depends on membrane cholesterol depletion and decreased order. By contrast, Piezo1 is inhibited by the athero-protective free docosahexaenoic acid, either without or with 7-KC. Altogether, these findings indicate that macrophage Piezo1 is differentially modulated by pro- and anti-atherogenic lipids, pointing to the role of Piezo1 and its potentiation by oxysterols in atherosclerosis.
Collapse
Affiliation(s)
- Edyta Glogowska
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Gregor P Jose
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Ana Rita Dias Araújo
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Malika Arhatte
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Raphael Divita
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Coraline Borowczyk
- Institut National de la Santé et de la Recherche Médicale, Inserm, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, Nice, France
| | - Thibault Barouillet
- Institut National de la Santé et de la Recherche Médicale, Inserm, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, Nice, France
| | - Baile Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China
| | - Frédéric Brau
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Rémi Peyronnet
- Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg - Bad Krozingen, Medical Center - University of Freiburg and Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Amanda Patel
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Bruno Mesmin
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Takeshi Harayama
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Bruno Antonny
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France
| | - Aimin Xu
- State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China
| | - Laurent Yvan-Charvet
- Institut National de la Santé et de la Recherche Médicale, Inserm, Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Atip-Avenir, Fédération Hospitalo-Universitaire (FHU) Oncoage, Nice, France
| | - Eric Honoré
- Université Côte d'Azur, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST, 06560 Valbonne, France; State Key Laboratory of Pharmaceutical Biotechnology, Department of Medicine and Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China.
| |
Collapse
|
|
2
|
Shukla A, Sharma C, Malik MZ, Singh AK, Aditya AK, Mago P, Shalimar, Ray AK. Deciphering the tripartite interaction of urbanized environment, gut microbiome and cardio-metabolic disease. JOURNAL OF ENVIRONMENTAL MANAGEMENT 2025; 377:124693. [PMID: 40022791 DOI: 10.1016/j.jenvman.2025.124693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/13/2025] [Accepted: 02/21/2025] [Indexed: 03/04/2025]
Abstract
The world is experiencing a sudden surge in urban population, especially in developing Asian and African countries. Consequently, the global burden of cardio-metabolic disease (CMD) is also rising owing to gut microbiome dysbiosis due to urbanization factors such as mode of birth, breastfeeding, diet, environmental pollutants, and soil exposure. Dysbiotic gut microbiome indicated by altered Firmicutes to Bacteroides ratio and loss of beneficial short-chain fatty acids-producing bacteria such as Prevotella, and Ruminococcus may disrupt host-intestinal homeostasis by altering host immune response, gut barrier integrity, and microbial metabolism through altered T-regulatory cells/T-helper cells balance, activation of pattern recognition receptors and toll-like receptors, decreased mucus production, elevated level of trimethylamine-oxide and primary bile acids. This leads to a pro-inflammatory gut characterized by increased pro-inflammatory cytokines such as tumour necrosis factor-α, interleukin-2, Interferon-ϒ and elevated levels of metabolites or metabolic endotoxemia due to leaky gut formation. These pathophysiological characteristics are associated with an increased risk of cardio-metabolic disease. This review aims to comprehensively elucidate the effect of urbanization on gut microbiome-driven cardio-metabolic disease. Additionally, it discusses targeting the gut microbiome and its associated pathways via strategies such as diet and lifestyle modulation, probiotics, prebiotics intake, etc., for the prevention and treatment of disease which can potentially be integrated into clinical and professional healthcare settings.
Collapse
Affiliation(s)
- Avaneesh Shukla
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Chanchal Sharma
- Department of Environmental Studies, University of Delhi, New Delhi, India
| | - Md Zubbair Malik
- Department of Translational Medicine, Dasman Diabetes Institute, Kuwait City, Kuwait
| | - Alok Kumar Singh
- Department of Zoology, Ramjas College, University of Delhi, New Delhi, India
| | - Abhishek Kumar Aditya
- Department of Medicine, K.D. Medical College, Hospital and Research Center, Mathura, India
| | - Payal Mago
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi, India; Campus of Open Learning, University of Delhi, New Delhi, India
| | - Shalimar
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ashwini Kumar Ray
- Department of Environmental Studies, University of Delhi, New Delhi, India.
| |
Collapse
|
|
3
|
Ghavidel F, Hashemy SI, Aliari M, Rajabian A, Tabrizi MH, Atkin SL, Jamialahmadi T, Hosseini H, Sahebkar A. The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders. Curr Med Chem 2025; 32:2219-2234. [PMID: 37828670 DOI: 10.2174/0109298673255218231005062112] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 06/25/2023] [Accepted: 08/26/2023] [Indexed: 10/14/2023]
Abstract
Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.
Collapse
Affiliation(s)
- Farideh Ghavidel
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Isaac Hashemy
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdeyeh Aliari
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arezoo Rajabian
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Stephen L Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Tannaz Jamialahmadi
- International UNESCO center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hossein Hosseini
- Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
|
4
|
Fliri A, Kajiji S. Effects of vitamin D signaling in cardiovascular disease: centrality of macrophage polarization. Front Cardiovasc Med 2024; 11:1388025. [PMID: 38984353 PMCID: PMC11232491 DOI: 10.3389/fcvm.2024.1388025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 05/24/2024] [Indexed: 07/11/2024] Open
Abstract
Among the leading causes of natural death are cardiovascular diseases, cancer, and respiratory diseases. Factors causing illness include genetic predisposition, aging, stress, chronic inflammation, environmental factors, declining autophagy, and endocrine abnormalities including insufficient vitamin D levels. Inconclusive clinical outcomes of vitamin D supplements in cardiovascular diseases demonstrate the need to identify cause-effect relationships without bias. We employed a spectral clustering methodology capable of analyzing large diverse datasets for examining the role of vitamin D's genomic and non-genomic signaling in disease in this study. The results of this investigation showed the following: (1) vitamin D regulates multiple reciprocal feedback loops including p53, macrophage autophagy, nitric oxide, and redox-signaling; (2) these regulatory schemes are involved in over 2,000 diseases. Furthermore, the balance between genomic and non-genomic signaling by vitamin D affects autophagy regulation of macrophage polarization in tissue homeostasis. These findings provide a deeper understanding of how interactions between genomic and non-genomic signaling affect vitamin D pharmacology and offer opportunities for increasing the efficacy of vitamin D-centered treatment of cardiovascular disease and healthy lifespans.
Collapse
Affiliation(s)
- Anton Fliri
- Emergent System Analytics LLC, Clinton, CT, United States
| | - Shama Kajiji
- Emergent System Analytics LLC, Clinton, CT, United States
| |
Collapse
|
|
5
|
Kim JM, Kim JW, Kang HJ, Choi W, Lee JY, Kim SW, Shin IS, Ahn Y, Jeong MH. Identification of depression in patients with acute coronary syndrome using multiple serum biomarkers. Gen Hosp Psychiatry 2024; 88:1-9. [PMID: 38428184 DOI: 10.1016/j.genhosppsych.2024.02.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 02/21/2024] [Accepted: 02/21/2024] [Indexed: 03/03/2024]
Abstract
BACKGROUND Biomarkers for depression in patients with acute coronary syndrome (ACS) have not been identified. METHODS This study evaluated multiple serum biomarkers for depressive disorders after ACS. Thirteen serum biomarkers associated with seven functional systems, along with sociodemographic/clinical characteristics, were evaluated in 969 patients within 2 weeks after ACS onset (acute phase). In total, 711 patients were evaluated for depressive disorder using DSM-IV criteria 1 year later (chronic phase). Logistic regression was used for the analysis. RESULTS Depressive disorders were observed in 378 patients (39.0%) in the acute phase of ACS and 183 patients (25.7%) in the chronic phase. The weighted scores of five serum biomarkers (high-sensitivity C-reactive protein, interleukin-6, homocysteine, troponin I, and creatine kinase-MB) were significantly associated with depressive disorder diagnosis in the acute phase, and the weighted scores of three other biomarkers (tumor necrosis factor-alpha, interleukin-1 beta, and homocysteine) were significantly associated with depressive disorders in the chronic phase, in a dose-dependent manner after adjusting for relevant covariates (all P-values <0.001). CONCLUSIONS The combination of several serum biomarkers exhibited robust associations with depressive disorders in both the acute and chronic phases of ACS.
Collapse
Affiliation(s)
- Jae-Min Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea.
| | - Ju-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Hee-Ju Kang
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Wonsuk Choi
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Republic of Korea
| | - Ju-Yeon Lee
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Sung-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Il-Seon Shin
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Youngkeun Ahn
- Department of Cardiology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Myung Ho Jeong
- Department of Cardiology, Chonnam National University Medical School, Gwangju, Republic of Korea
| |
Collapse
|
|
6
|
Zhang X, King C, Dowell A, Moss P, Harper L, Chanouzas D, Ruan XZ, Salama AD. CD36 regulates macrophage and endothelial cell activation and multinucleate giant cell formation in anti neutrophil cytoplasm antibody vasculitis. Clin Immunol 2024; 260:109914. [PMID: 38286173 DOI: 10.1016/j.clim.2024.109914] [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: 10/07/2023] [Revised: 01/17/2024] [Accepted: 01/19/2024] [Indexed: 01/31/2024]
Abstract
OBJECTIVE To investigate CD36 in ANCA-associated vasculitis (AAV), a condition characterized by monocyte/macrophage activation and vascular damage. METHODS CD36 expression was assessed in AAV patients and healthy controls (HC). The impact of palmitic acid (PA) stimulation on multinucleate giant cell (MNGC) formation, macrophage, and endothelial cell activation, with or without CD36 knockdown, was examined. RESULTS CD36 was overexpressed on AAV patients' monocytes compared to HC, regardless of disease activity. AAV patients exhibited elevated soluble CD36 levels in serum and plasma and PR3-ANCA patients' monocytes demonstrated increased MNGC formation following PA stimulation compared to HC. PA stimulation of macrophages or endothelial cells resulted in heightened CD36 expression, cell activation, increased macrophage migration inhibitory factor (MIF) production, and c-Myc expression, with attenuation upon CD36 knockdown. CONCLUSION CD36 participates in macrophage and endothelial cell activation and MNGC formation, features of AAV pathogenesis. AAV treatment may involve targeting CD36 or MIF.
Collapse
Affiliation(s)
- Xiang Zhang
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, London, UK
| | - Catherine King
- Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK
| | - Alexander Dowell
- Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK
| | - Paul Moss
- Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK
| | - Lorraine Harper
- Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK
| | - Dimitrios Chanouzas
- Institute of Immunology and Immunotherapy, College of Medical & Dental Sciences University of Birmingham, Birmingham, UK
| | - Xiong-Zhong Ruan
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, London, UK
| | - Alan David Salama
- UCL Centre for Kidney and Bladder Health, Royal Free Hospital, London, UK.
| |
Collapse
|
|
7
|
Lam CW, Castranova V, Driscoll K, Warheit D, Ryder V, Zhang Y, Zeidler-Erdely P, Hunter R, Scully R, Wallace W, James J, Crucian B, Nelman M, McCluskey R, Gardner D, Renne R, McClellan R. A review of pulmonary neutrophilia and insights into the key role of neutrophils in particle-induced pathogenesis in the lung from animal studies of lunar dusts and other poorly soluble dust particles. Crit Rev Toxicol 2023; 53:441-479. [PMID: 37850621 PMCID: PMC10872584 DOI: 10.1080/10408444.2023.2258925] [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] [Received: 03/09/2023] [Revised: 08/25/2023] [Accepted: 08/27/2023] [Indexed: 10/19/2023]
Abstract
The mechanisms of particle-induced pathogenesis in the lung remain poorly understood. Neutrophilic inflammation and oxidative stress in the lung are hallmarks of toxicity. Some investigators have postulated that oxidative stress from particle surface reactive oxygen species (psROS) on the dust produces the toxicopathology in the lungs of dust-exposed animals. This postulate was tested concurrently with the studies to elucidate the toxicity of lunar dust (LD), which is believed to contain psROS due to high-speed micrometeoroid bombardment that fractured and pulverized lunar surface regolith. Results from studies of rats intratracheally instilled (ITI) with three LDs (prepared from an Apollo-14 lunar regolith), which differed 14-fold in levels of psROS, and two toxicity reference dusts (TiO2 and quartz) indicated that psROS had no significant contribution to the dusts' toxicity in the lung. Reported here are results of further investigations by the LD toxicity study team on the toxicological role of oxidants in alveolar neutrophils that were harvested from rats in the 5-dust ITI study and from rats that were exposed to airborne LD for 4 weeks. The oxidants per neutrophils and all neutrophils increased with dose, exposure time and dust's cytotoxicity. The results suggest that alveolar neutrophils play a critical role in particle-induced injury and toxicity in the lung of dust-exposed animals. Based on these results, we propose an adverse outcome pathway (AOP) for particle-associated lung disease that centers on the crucial role of alveolar neutrophil-derived oxidant species. A critical review of the toxicology literature on particle exposure and lung disease further supports a neutrophil-centric mechanism in the pathogenesis of lung disease and may explain previously reported animal species differences in responses to poorly soluble particles. Key findings from the toxicology literature indicate that (1) after exposures to the same dust at the same amount, rats have more alveolar neutrophils than hamsters; hamsters clear more particles from their lungs, consequently contributing to fewer neutrophils and less severe lung lesions; (2) rats exposed to nano-sized TiO2 have more neutrophils and more severe lesions in their lungs than rats exposed to the same mass-concentration of micron-sized TiO2; nano-sized dust has a greater number of particles and a larger total particle-cell contact surface area than the same mass of micron-sized dust, which triggers more alveolar epithelial cells (AECs) to synthesize and release more cytokines that recruit a greater number of neutrophils leading to more severe lesions. Thus, we postulate that, during chronic dust exposure, particle-inflicted AECs persistently release cytokines, which recruit neutrophils and activate them to produce oxidants resulting in a prolonged continuous source of endogenous oxidative stress that leads to lung toxicity. This neutrophil-driven lung pathogenesis explains why dust exposure induces more severe lesions in rats than hamsters; why, on a mass-dose basis, nano-sized dusts are more toxic than the micron-sized dusts; why lung lesions progress with time; and why dose-response curves of particle toxicity exhibit a hockey stick like shape with a threshold. The neutrophil centric AOP for particle-induced lung disease has implications for risk assessment of human exposures to dust particles and environmental particulate matter.
Collapse
Affiliation(s)
- Chiu-wing Lam
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
- Biomedical & Environmental Research Department, KBR Toxicology & Environmental Chemistry, Houston, TX, USA
- Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX, USA
| | - Vincent Castranova
- Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
| | - Kevin Driscoll
- Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA
| | | | - Valerie Ryder
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
| | - Ye Zhang
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
- Utilization and Life Sciences Office, Kennedy Space Center, Merritt Island, FL, USA
| | - Patti Zeidler-Erdely
- Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA
| | - Robert Hunter
- Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX, USA
| | - Robert Scully
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
- Biomedical & Environmental Research Department, KBR Toxicology & Environmental Chemistry, Houston, TX, USA
| | - William Wallace
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
- Biomedical & Environmental Research Department, KBR Toxicology & Environmental Chemistry, Houston, TX, USA
| | - John James
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
| | - Brian Crucian
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
| | - Mayra Nelman
- Biomedical Research and Environmental Sciences Division, NASA Johnson Space Center, Houston, TX, USA
- Biomedical & Environmental Research Department, KBR Toxicology & Environmental Chemistry, Houston, TX, USA
| | | | | | - Roger Renne
- Roger Renne ToxPath Consulting Inc., Sumner, WA, USA
| | - Roger McClellan
- Toxicology and Human Health Risk Analysis, Albuquerque, NM, USA
| |
Collapse
|
|
8
|
Duan H, Wang L, Huangfu M, Li H. The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials. Biomed Pharmacother 2023; 165:115276. [PMID: 37542852 DOI: 10.1016/j.biopha.2023.115276] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/07/2023] Open
Abstract
Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players in various biological processes. Recent research has revealed their significant functions in immune and inflammatory responses. For instance, butyrate reduces the development of interferon-gamma (IFN-γ) generating cells while promoting the development of regulatory T (Treg) cells. Propionate inhibits the initiation of a Th2 immune response by dendritic cells (DCs). Notably, SCFAs have an inhibitory impact on the polarization of M2 macrophages, emphasizing their immunomodulatory properties and potential for therapeutics. In animal models of asthma, both butyrate and propionate suppress the M2 polarization pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis of gut microbiota leading to altered SCFA production has been implicated in prostate cancer progression. SCFAs trigger autophagy in cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. Manipulating microbiota- producing SCFAs holds promise for cancer treatment. Additionally, SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. This highlights the antimicrobial potential of SCFAs and their role in host defense mechanisms. This comprehensive review provides an in-depth analysis of the latest research on the functional aspects and underlying mechanisms of SCFAs in relation to macrophage activities in a wide range of diseases, including infectious diseases and cancers. By elucidating the intricate interplay between SCFAs and macrophage functions, this review aims to contribute to the understanding of their therapeutic potential and pave the way for future interventions targeting SCFAs in disease management.
Collapse
Affiliation(s)
- Hongliang Duan
- Department of Thyroid Surgery, the Second Hospital of Jilin University, Changchun 130000, China
| | - LiJuan Wang
- Department of Endocrinology, the Second Hospital of Jilin University, Changchun 130000, China.
| | - Mingmei Huangfu
- Department of Thyroid Surgery, the Second Hospital of Jilin University, Changchun 130000, China
| | - Hanyang Li
- Department of Endocrinology, the Second Hospital of Jilin University, Changchun 130000, China
| |
Collapse
|
|
9
|
Guo J, Hu Z, Ren L, Zhao W, Zuo R, Guo S, Jia C, Gao W. Circulating tumor necrosis factor-α, interleukin-1β, and interleukin-17A estimates increased major adverse cardiac event risk in acute myocardial infarction patients. J Clin Lab Anal 2023; 37:e24853. [PMID: 36877748 PMCID: PMC10098063 DOI: 10.1002/jcla.24853] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 02/07/2023] [Accepted: 02/12/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Inflammatory cytokines are implicated in the development of atherosclerosis and cardiomyocyte injury during acute myocardial infarction (AMI). This study aimed to investigate the correlation of eight common inflammatory cytokines with major adverse cardiac event (MACE) risk and further establish a prognostic model in AMI patients. METHODS Serum samples of 210 AMI patients and 20 angina pectoris patients were, respectively, collected at admission, to detect tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) via enzyme-linked immunosorbent assay. RESULTS TNF-α, IL-6, IL-8, IL-17A, VCAM-1, and ICAM-1 were elevated (all p < 0.050); IL-10 (p = 0.009) was declined; IL-1β (p = 0.086) was not varied in AMI patients compared with angina pectoris patients. TNF-α (p = 0.008), IL-17A (p = 0.003), and VCAM-1 (p = 0.014) were elevated in patients with MACE occurrence compared to patients without MACE occurrence; meanwhile, they possessed a relatively good value for identifying MACE risk via receiver-operating characteristic (ROC) analysis. Subsequent multivariate logistic regression analysis revealed that the independent risk factors for MACE contained TNF-α (odds ratio (OR) = 1.038, p < 0.001), IL-1β (OR = 1.705, p = 0.044), IL-17A (OR = 1.021, p = 0.009), history of diabetes mellitus (OR = 4.188, p = 0.013), history of coronary heart disease (OR = 3.287, p = 0.042), and symptom-to-balloon time (OR = 1.064, p = 0.030), whose combination disclosed a satisfying prognostic value for MACE risk (area under the curve: 0.877, 95% CI: 0.817-0.936). CONCLUSION Elevated levels of serum TNF-α, IL-1β, and IL-17A independently correlated with MACE risk in AMI patients, which perhaps provide novel auxiliary for AMI prognostic prediction.
Collapse
Affiliation(s)
- Jing Guo
- Department of Cardiology, HanDan Central Hospital, Handan, China
| | - Zhenfeng Hu
- Department of General Surgery (Department of Plastic Surgery), Affiliated Hospital of Hebei University of Engineering, Handan, China
| | - Liang Ren
- Emergency Department, Handan Central Hospital, Handan, China
| | - Weibo Zhao
- Emergency Department, Handan Central Hospital, Handan, China
| | - Ruijing Zuo
- Emergency Department, Handan Central Hospital, Handan, China
| | - Shuang Guo
- Emergency Department, Handan Central Hospital, Handan, China
| | - Chaoguo Jia
- Emergency Department, Handan Central Hospital, Handan, China
| | - Wei Gao
- Emergency Department, Handan Central Hospital, Handan, China
| |
Collapse
|
|
10
|
Hazra J, Vijayakumar A, Mahapatra NR. Emerging role of heat shock proteins in cardiovascular diseases. ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY 2023; 134:271-306. [PMID: 36858739 DOI: 10.1016/bs.apcsb.2022.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Heat Shock Proteins (HSPs) are evolutionarily conserved proteins from prokaryotes to eukaryotes. They are ubiquitous proteins involved in key physiological and cellular pathways (viz. inflammation, immunity and apoptosis). Indeed, the survivability of the cells under various stressful conditions depends on appropriate levels of HSP expression. There is a growing line of evidence for the role of HSPs in regulating cardiovascular diseases (CVDs) (viz. hypertension, atherosclerosis, atrial fibrillation, cardiomyopathy and heart failure). Furthermore, studies indicate that a higher concentration of circulatory HSP antibodies correlate to CVDs; some are even potential markers for CVDs. The multifaceted roles of HSPs in regulating cellular signaling necessitate unraveling their links to pathophysiology of CVDs. This review aims to consolidate our understanding of transcriptional (via multiple transcription factors including HSF-1, NF-κB, CREB and STAT3) and post-transcriptional (via microRNAs including miR-1, miR-21 and miR-24) regulation of HSPs. The cytoprotective nature of HSPs catapults them to the limelight as modulators of cell survival. Yet another attractive prospect is the development of new therapeutic strategies against cardiovascular diseases (from hypertension to heart failure) by targeting the regulation of HSPs. Moreover, this review provides insights into how genetic variation of HSPs can contribute to the manifestation of CVDs. It would also offer a bird's eye view of the evolving role of different HSPs in the modulation and manifestation of cardiovascular disease.
Collapse
Affiliation(s)
- Joyita Hazra
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India
| | - Anupama Vijayakumar
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India
| | - Nitish R Mahapatra
- Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, India.
| |
Collapse
|
|
11
|
Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases. Nutrients 2023; 15:nu15030607. [PMID: 36771313 PMCID: PMC9921390 DOI: 10.3390/nu15030607] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/09/2023] [Accepted: 01/20/2023] [Indexed: 01/26/2023] Open
Abstract
Gut microbiota is the largest and most complex microflora in the human body, which plays a crucial role in human health and disease. Over the past 20 years, the bidirectional communication between gut microbiota and extra-intestinal organs has been extensively studied. A better comprehension of the alternative mechanisms for physiological and pathophysiological processes could pave the way for health. Cardiovascular disease (CVD) is one of the most common diseases that seriously threatens human health. Although previous studies have shown that cardiovascular diseases, such as heart failure, hypertension, and coronary atherosclerosis, are closely related to gut microbiota, limited understanding of the complex pathogenesis leads to poor effectiveness of clinical treatment. Dysregulation of inflammation always accounts for the damaged gastrointestinal function and deranged interaction with the cardiovascular system. This review focuses on the characteristics of gut microbiota in CVD and the significance of inflammation regulation during the whole process. In addition, strategies to prevent and treat CVD through proper regulation of gut microbiota and its metabolites are also discussed.
Collapse
|
|
12
|
The role of vessel wall imaging in determining the best treatment approach for coexisting aneurysms and subarachnoid hemorrhage. Acta Neurol Belg 2022:10.1007/s13760-022-02096-8. [PMID: 36173550 DOI: 10.1007/s13760-022-02096-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 09/12/2022] [Indexed: 11/01/2022]
Abstract
PURPOSE The purpose of this study was to investigate the utilization of gadolinium enhancement on vessel wall imaging (VWI) in treatment decision-making for patients with two intracranial aneurysms presenting as a subarachnoid hemorrhage (SAH). MATERIALS AND METHODS We prospectively performed VWI using 3.0-Tesla (3T) magnetic resonance imaging (MRI) before treatment with endovascular coiling or surgical clipping in patients with one or two intracranial aneurysms. The VWI protocol includes three different scans: black blood (BB) T1-weighted, BB T2-weighted, TOF axial, and BB contrast-enhanced T1-weighted imaging. We analyzed all aneurysm ruptures both with and without gadolinium enhancement of the aneurysm wall. RESULTS Thirty-eight patients with 48 aneurysms were enrolled in this study. Of these patients, 28 had a single aneurysm (15 ruptured and 13 unruptured), and 10 had two aneurysms and SAH (9 patients with two aneurysms and 1 patient with three aneurysms). Of the 15 single ruptured aneurysms, 12 (80.0%) showed positive wall enhancement, whereas 2 of the 13 single unruptured aneurysms (15.4%) demonstrated positive wall enhancement. Ten patients with SAH and two aneurysms showed wall enhancement of a single aneurysm, and these aneurysms were treated first. CONCLUSION Gadolinium enhancement of an aneurysm wall on MRI was associated with aneurysm rupture. In patients with two aneurysms and SAH, this type of imaging can play an important role in determining the order of aneurysm treatment.
Collapse
|
|
13
|
Chu X, Lu Y, Mei M, Peng P, Zhao Y, Fu G, Qiu F, Jin C. Correlation Between Serum Uric Acid Levels and Coronary Plaque Characteristics on Optical Coherence Tomography. Int Heart J 2022; 63:806-813. [PMID: 36104242 DOI: 10.1536/ihj.21-826] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Elevated serum uric acid (sUA) is associated with increasing risk of coronary heart disease (CHD). However, existing research is limited by potential confounders. Herein, our study aims to probe the association between sUA levels and the morphological characteristics of coronary plaque by a propensity score matching (PSM) analysis.All 420 patients with CHD who had undergone optical coherence tomography of culprit lesions were included. Eligible patients were assigned into 2 groups according to sUA level: high-sUA group (sUA ≥ 6.0 mg/dL) and low-sUA group (sUA < 6.0 mg/dL). PSM was applied to control the balance of baseline characteristics.After PSM, a total of 112 patients were included in our study (56 in each group). The high-sUA group showed a higher prevalence of TCFA (35.7% versus 16.1%, P = 0.03) and macrophage infiltration (33.9% versus 14.3%, P = 0.026) compared with the low-sUA group. Plaques in the high-sUA group had a wider maximum lipid arc (166.51° (115.77°, 224.14°) versus 142.29° (93.95°, 169.06°), P = 0.048), longer calcification length (6.77 (3.90, 20.55) mm versus 4.20 (1.95, 7.45) mm, P = 0.040), and thinner minimum fibrous cap thickness (43.81 (28.17, 62.26) μm versus 92.57 (46.25, 135.37) μm, P = 0.003). Correlation analysis indicated that the sUA value was inversely associated with the minimum fibrous cap thickness (r = -0.332, P = 0.015) and positively associated with the maximum lipid arc (r = 0.399, P = 0.003), average lipid arc (r = 0.347, P = 0.011), and calcification length (r = 0.386, P = 0.006).The relationship between high-sUA levels and typical vulnerable features of plaques persisted after balancing the traditional risk factors.
Collapse
Affiliation(s)
- Xiaopeng Chu
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Yanli Lu
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Menghan Mei
- Department of Blood Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College
| | - Peng Peng
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Yanbo Zhao
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Guosheng Fu
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Fuyu Qiu
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Chongying Jin
- Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| |
Collapse
|
|
14
|
Mandal M, Madeira M, Amin R, Buevich AV, Cheng A, Labroli M, Liu X, Acton J, Pio B, Basso A, Chobanian H, Dong G, Dropinski J, Guo Y, Guo Z, Kurowski S, Korfmacher W, Lee S, Meng D, Ondeyka D, Yang Z, Zhang R, Wei H, Wu Z, Zhang F, Wollenberg G, Biftu T, Greenlee WJ, Chintala M, Maletic M, Zhu Z. Lead Optimization to Advance Protease-Activated Receptor-1 Antagonists in Early Discovery. J Med Chem 2022; 65:5575-5592. [DOI: 10.1021/acs.jmedchem.1c02048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
15
|
Farahi L, Sinha SK, Lusis AJ. Roles of Macrophages in Atherogenesis. Front Pharmacol 2021; 12:785220. [PMID: 34899348 PMCID: PMC8660976 DOI: 10.3389/fphar.2021.785220] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/04/2021] [Indexed: 12/18/2022] Open
Abstract
Atherosclerosis is a chronic inflammatory disease that may ultimately lead to local proteolysis, plaque rupture, and thrombotic vascular disease, resulting in myocardial infarction, stroke, and sudden cardiac death. Circulating monocytes are recruited to the arterial wall in response to inflammatory insults and differentiate into macrophages which make a critical contribution to tissue damage, wound healing, and also regression of atherosclerotic lesions. Within plaques, macrophages take up aggregated lipoproteins which have entered the vessel wall to give rise to cholesterol-engorged foam cells. Also, the macrophage phenotype is influenced by various stimuli which affect their polarization, efferocytosis, proliferation, and apoptosis. The heterogeneity of macrophages in lesions has recently been addressed by single-cell sequencing techniques. This article reviews recent advances regarding the roles of macrophages in different stages of disease pathogenesis from initiation to advanced atherosclerosis. Macrophage-based therapies for atherosclerosis management are also described.
Collapse
Affiliation(s)
- Lia Farahi
- Monoclonal Antibody Research Center, Avicenna Research Institute, Tehran, Iran
| | - Satyesh K. Sinha
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Aldons J. Lusis
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| |
Collapse
|
|
16
|
De Negri Atanasio G, Ferrari PF, Campardelli R, Perego P, Palombo D. Innovative nanotools for vascular drug delivery: the atherosclerosis case study. J Mater Chem B 2021; 9:8558-8568. [PMID: 34609399 DOI: 10.1039/d1tb01071a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cardiovascular diseases are the leading cause of mortality in the Western world. Among them, atherosclerosis represents one of the most common diseases in the modern society due to a common sedentary lifestyle, high-fat diet, and smoking. In the near future, a new approach could potentially improve the therapy of vascular pathologies, where to date the non-specific treatments present several limitations, such as poor biodistribution, quick elimination from the body, and undesired side-effects. In this field, nanotechnology has a great potential for the therapy and diagnosis of atherosclerosis with more and more recent and innovative publications. This review is a critical analysis of the results reported in the literature regarding the different and possible new approaches for the therapy and diagnosis of atherosclerosis.
Collapse
Affiliation(s)
- Giulia De Negri Atanasio
- Department of Experimental Medicine, University of Genoa, via Leon Battista Alberti, 2, 16132 Genoa, Italy
| | - Pier Francesco Ferrari
- Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy
| | - Roberta Campardelli
- Department of Civil, Chemical and Environmental Engineering, University of Genoa, via Opera Pia, 15, 16145 Genoa, Italy.
| | - Patrizia Perego
- Department of Civil, Chemical and Environmental Engineering, University of Genoa, via Opera Pia, 15, 16145 Genoa, Italy. .,Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, via Montallegro, 1, 16145 Genoa, Italy
| | - Domenico Palombo
- Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy.,Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, via Montallegro, 1, 16145 Genoa, Italy.,Vascular and Endovascular Surgery Unit, IRCCS Ospedale Policlinico San Martino, largo Rosanna Benzi, 10, 16132 Genoa, Italy
| |
Collapse
|
|
17
|
Wen CJ, Chang CH, Chen CY, Peng JK, Huang HL, Chuang PN, Chen CY, Tsai JS. Age-dependent messenger RNA expression of toll-like receptor 4 and intercellular adhesion molecule-1 in peripheral blood mononuclear cells. Eur J Clin Invest 2021; 51:e13522. [PMID: 33590878 DOI: 10.1111/eci.13522] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 02/13/2021] [Accepted: 02/14/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND Inflammation plays an important role in the ageing process in which monocytes/macrophages are important players. Intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor-α (TNF-α) and Toll-like receptor 4 (TLR4) are well-known inflammatory markers. This study aimed to investigate the relationship between age and the expression and correlation of ICAM-1, TNF-α and TLR4 mRNA in peripheral blood mononuclear cells (PBMCs). METHODS A total of 239 participants were recruited in a medical centre in Taiwan. The mRNA isolated from the PBMCs was used to determine the levels of ICAM-1, TNF-α and TLR4 mRNAs with real-time polymerase chain reaction (PCR). The propensity-matched analysis was also applied for subgroup analysis. RESULTS When compared 189 older adults (≧65 years) to 50 younger adults (<65 years), the ICAM-1, TNF-α and TLR4 mRNA levels in PBMCs were significantly higher in older adults (2.00 ± 0.72 vs 0.87 ± 0.34 for ICAM-1, 2.32 ± 0.69 vs 1.15 ± 0.44 for TNF-α and 1.56 ± 0.47 vs 1.05 ± 0.51 for TLR4, and all P < .0001). Also, both age and TLR4 were independent factors affecting mononuclear cell ICAM-1 in the multiple linear regression analysis (P < .0001). CONCLUSION The mRNA levels of ICAM-1 and TLR4 in PBMCs are higher in older adults than those in younger adults. TLR4 is an independent factor affecting ICAM-1 expression in PBMCs, especially in older adults. This may suggest that ICAM-1 and TLR4 in PBMCs are potential biomarkers and their relationship may shed some light on the ageing process.
Collapse
Affiliation(s)
- Chiung-Jung Wen
- Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan.,Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chin-Hao Chang
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chin-Ying Chen
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jen-Kuei Peng
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsien-Liang Huang
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Ni Chuang
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Yu Chen
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Division of Geriatric Research, Institute of Population Health Science, National Health Research Institutes, Zhunan, Taiwan
| | - Jaw-Shiun Tsai
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
18
|
Mettu PS, Allingham MJ, Cousins SW. Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities. Prog Retin Eye Res 2021; 82:100906. [PMID: 33022379 PMCID: PMC10368393 DOI: 10.1016/j.preteyeres.2020.100906] [Citation(s) in RCA: 201] [Impact Index Per Article: 50.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 09/18/2020] [Accepted: 09/22/2020] [Indexed: 12/13/2022]
Abstract
Intravitreal anti-vascular endothelial growth factor (VEGF) drugs have revolutionized the treatment of neovascular age-related macular degeneration (NVAMD). However, many patients suffer from incomplete response to anti-VEGF therapy (IRT), which is defined as (1) persistent (plasma) fluid exudation; (2) unresolved or new hemorrhage; (3) progressive lesion fibrosis; and/or (4) suboptimal vision recovery. The first three of these collectively comprise the problem of persistent disease activity (PDA) in spite of anti-VEGF therapy. Meanwhile, the problem of suboptimal vision recovery (SVR) is defined as a failure to achieve excellent functional visual acuity of 20/40 or better in spite of sufficient anti-VEGF treatment. Thus, incomplete response to anti-VEGF therapy, and specifically PDA and SVR, represent significant clinical unmet needs. In this review, we will explore PDA and SVR in NVAMD, characterizing the clinical manifestations and exploring the pathobiology of each. We will demonstrate that PDA occurs most frequently in NVAMD patients who develop high-flow CNV lesions with arteriolarization, in contrast to patients with capillary CNV who are highly responsive to anti-VEGF therapy. We will review investigations of experimental CNV and demonstrate that both types of CNV can be modeled in mice. We will present and consider a provocative hypothesis: formation of arteriolar CNV occurs via a distinct pathobiology, termed neovascular remodeling (NVR), wherein blood-derived macrophages infiltrate the incipient CNV lesion, recruit bone marrow-derived mesenchymal precursor cells (MPCs) from the circulation, and activate MPCs to become vascular smooth muscle cells (VSMCs) and myofibroblasts, driving the development of high-flow CNV with arteriolarization and perivascular fibrosis. In considering SVR, we will discuss the concept that limited or poor vision in spite of anti-VEGF may not be caused simply by photoreceptor degeneration but instead may be associated with photoreceptor synaptic dysfunction in the neurosensory retina overlying CNV, triggered by infiltrating blood-derived macrophages and mediated by Müller cell activation Finally, for each of PDA and SVR, we will discuss current approaches to disease management and treatment and consider novel avenues for potential future therapies.
Collapse
Affiliation(s)
- Priyatham S Mettu
- Duke Center for Macular Diseases, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, NC.
| | - Michael J Allingham
- Duke Center for Macular Diseases, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, NC
| | - Scott W Cousins
- Duke Center for Macular Diseases, Department of Ophthalmology, Duke University School of Medicine, Durham, NC, NC; Department of Immunology, Duke University School of Medicine, Durham, NC, USA
| |
Collapse
|
|
19
|
Suzuki H, Mikami T, Iwahara N, Akiyama Y, Wanibuchi M, Komatsu K, Yokoyama R, Hirano T, Hosoda R, Horio Y, Kuno A, Mikuni N. Aging-associated inflammation and fibrosis in arachnoid membrane. BMC Neurol 2021; 21:169. [PMID: 33882882 PMCID: PMC8058966 DOI: 10.1186/s12883-021-02202-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 04/13/2021] [Indexed: 11/16/2024] Open
Abstract
Background The physiological and pathological significance of the arachnoid membrane (AM) is still unknown. In this study, we investigated various characteristics of the AM, focusing on the influence of inflammation and fibrosis. Methods Small pieces of AM sample were obtained during neurosurgical procedures from 74 cases. The clinical and pathological characteristics of the hyperplastic AM group (≥ 50 μm) and the non-hyperplastic AM group (< 50 μm) were compared. Then, potential correlations between AM thickness and clinical characteristics were analyzed. Moreover, VEGFα, TGFβ, and TGFα levels were quantitated by real time PCR. Then, the potential correlations between AM thickness and these inflammatory or anti-inflammatory markers, and the influence of the original disease were calculated. Results The median age of the patients in hyperplastic AM group was significantly older than that of the non-hyperplastic AM group. Moreover, the number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells in the hyperplastic AM group was significantly higher than that in the non-hyperplastic AM group. The AM thickness was significantly correlated to age and number of fibroblasts, CD68+ cells, CD86+ cells, and CD206+ cells. The thickness of the AM was significantly correlated to the messenger RNA expression levels of VEGFα (ρ = 0.337), and the VEGFα expression levels were significantly correlated with TGFβ and TNFα. Conclusions The AM hyperplasia was influenced by aging and could be a result of inflammation and fibrosis through cytokine secretion from the inflammatory cells and fibroblasts in the AM.
Collapse
Affiliation(s)
- Hime Suzuki
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Takeshi Mikami
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan.
| | - Naotoshi Iwahara
- Department of Pharmacology, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Yukinori Akiyama
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Masahiko Wanibuchi
- Department of Neurosurgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
| | - Katsuya Komatsu
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Rintaro Yokoyama
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Tsukasa Hirano
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Ryusuke Hosoda
- Department of Pharmacology, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Yoshiyuki Horio
- Department of Pharmacology, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Atsushi Kuno
- Department of Pharmacology, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Nobuhiro Mikuni
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| |
Collapse
|
|
20
|
Akhigbe R, Ajayi A. The impact of reactive oxygen species in the development of cardiometabolic disorders: a review. Lipids Health Dis 2021; 20:23. [PMID: 33639960 PMCID: PMC7916299 DOI: 10.1186/s12944-021-01435-7] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 01/26/2021] [Indexed: 02/07/2023] Open
Abstract
Oxidative stress, an alteration in the balance between reactive oxygen species (ROS) generation and antioxidant buffering capacity, has been implicated in the pathogenesis of cardiometabolic disorders (CMD). At physiological levels, ROS functions as signalling mediators, regulates various physiological functions such as the growth, proliferation, and migration endothelial cells (EC) and smooth muscle cells (SMC); formation and development of new blood vessels; EC and SMC regulated death; vascular tone; host defence; and genomic stability. However, at excessive levels, it causes a deviation in the redox state, mediates the development of CMD. Multiple mechanisms account for the rise in the production of free radicals in the heart. These include mitochondrial dysfunction and uncoupling, increased fatty acid oxidation, exaggerated activity of nicotinamide adenine dinucleotide phosphate oxidase (NOX), reduced antioxidant capacity, and cardiac metabolic memory. The purpose of this study is to discuss the link between oxidative stress and the aetiopathogenesis of CMD and highlight associated mechanisms. Oxidative stress plays a vital role in the development of obesity and dyslipidaemia, insulin resistance and diabetes, hypertension via various mechanisms associated with ROS-led inflammatory response and endothelial dysfunction.
Collapse
Affiliation(s)
- Roland Akhigbe
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria
- Reproductive Biology and Toxicology Research Laboratories, Oasis of Grace Hospital, Osogbo, Osun State Nigeria
- Department of Chemical Sciences, Kings University, Odeomu, Osun Nigeria
| | - Ayodeji Ajayi
- Department of Physiology, College of Medicine, Ladoke Akintola University of Technology, Ogbomoso, Oyo State Nigeria
| |
Collapse
|
|
21
|
Ferrari PF, Zattera E, Pastorino L, Perego P, Palombo D. Dextran/poly-L-arginine multi-layered CaCO 3-based nanosystem for vascular drug delivery. Int J Biol Macromol 2021; 177:548-558. [PMID: 33577822 DOI: 10.1016/j.ijbiomac.2021.02.058] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/31/2021] [Accepted: 02/07/2021] [Indexed: 12/26/2022]
Abstract
The development of heterogeneous drug delivery systems leads to innovative strategies for targeted therapy of common pathologies, such as cancer, immunological and neurological disorders. Nowadays, it is possible to choose among a great variety of nanoparticles on the basis of the needs they have to satisfy. However, a candidate for the treatment of cardiovascular pathologies is still missing. In this context, a targeted therapy implies the conceptualization of nanoparticles that take active part in the treatment of vascular pathologies. The aim of this work was to provide a method to produce multi-layered calcium carbonate (CaCO3) nanoparticles encapsulating a model protein, bovine serum albumin, with model antibodies on their surface. CaCO3 nanoparticles were produced by the combination of complex coacervation and mineralization and were engineered using layer-by-layer technique with a polysaccharide, dextran sulfate, and a homo-poly-amino acid, poly-L-arginine. Morphology, biocompatibility, cellular uptake, influence on cell expression of the inflammatory marker matrix metalloproteinase-9, and hemocompatibility of the nanoparticles were studied. The presence of the dextran/poly-L-arginine layers did not negatively affect the nanoparticle overall characteristics and they did not trigger proinflammatory response in vitro. Taking together all the obtained results, we consider the proposed CaCO3 nanoparticles as a promising tool in cardiovascular field.
Collapse
Affiliation(s)
- Pier Francesco Ferrari
- Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy.
| | - Elena Zattera
- Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy
| | - Laura Pastorino
- Department of Informatics, Bioengineering, Robotics and Systems Engineering, University of Genoa, via Opera Pia, 13, 16145 Genoa, Italy
| | - Patrizia Perego
- Department of Civil, Chemical and Environmental Engineering, University of Genoa, via Opera Pia, 15, 16145 Genoa, Italy; Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, via Montallegro, 1, 16145 Genoa, Italy
| | - Domenico Palombo
- Department of Surgical and Integrated Diagnostic Sciences, University of Genoa, viale Benedetto XV, 6, 16132 Genoa, Italy; Research Center for Biologically Inspired Engineering in Vascular Medicine and Longevity, University of Genoa, via Montallegro, 1, 16145 Genoa, Italy; Vascular and Endovascular Surgery Unit, IRCCS Ospedale Policlinico San Martino, largo Rosanna Benzi, 10, 16132 Genoa, Italy
| |
Collapse
|
|
22
|
Yu GR, Lee SJ, Kim DH, Lim DW, Kim H, Park WH, Kim JE. Literature-Based Drug Repurposing in Traditional Chinese Medicine: Reduced Inflammatory M1 Macrophage Polarization by Jisil Haebaek Gyeji-Tang Alleviates Cardiovascular Disease In Vitro and Ex Vivo. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:8881683. [PMID: 33456493 PMCID: PMC7787781 DOI: 10.1155/2020/8881683] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/13/2020] [Accepted: 11/24/2020] [Indexed: 12/20/2022]
Abstract
Relatively high proportions of proinflammatory M1-like macrophages in tissues may lead to vascular impairment and trigger numerous diseases including atherosclerosis-related cardiovascular disease (CVD). Jisil Haebaek Gyeji-tang (JHGT), a polyherbal decoction, is traditionally used to treat various human ailments including chest pain, angina, and myocardial infarction. In the present study, we investigated the anti-inflammatory effects of JHGT on lipopolysaccharide- (LPS-) stimulated M1 macrophage polarization generated via the mitogen-activated protein kinases (MAPKs) pathway in RAW 264.7 mouse macrophages. The reducing power of JHGT was also investigated using DAF-FA DA in a zebrafish model. JHGT significantly reduced inflammatory mediator levels, including iNOS, COX2, TNF-α, IL-6, and IL-1β, as compared with LPS-stimulated controls in vitro and ex vivo. Furthermore, JHGT suppressed the ERK1/2, JNK, and p38 MAPK pathways and reduced p-IκBα levels and the nuclear translocation of NF-κB in RAW 264.7 cells. In addition, treatment with JHGT significantly reduced the NO levels in LPS-treated zebrafish larva ex vivo. Our findings show the potent anti-inflammatory properties of JHGT are due to its suppression of MAPK signaling, NF-κB translocation, and M1 macrophage polarization.
Collapse
Affiliation(s)
- Ga-Ram Yu
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Seung-Jun Lee
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Da-Hoon Kim
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Dong-Woo Lim
- Department of Pathology, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Hyuck Kim
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
- Institute of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Won-Hwan Park
- Department of Diagnostics, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| | - Jai-Eun Kim
- Department of Pathology, College of Korean Medicine, Dongguk University, Dongguk-Ro 32, Goyang 10326, Republic of Korea
| |
Collapse
|
|
23
|
Qian S, Ma T, Zhang N, Liu X, Zhao P, Li X, Chen D, Hu L, Chang L, Xu L, Deng X, Fan Y. Spatiotemporal transfer of nitric oxide in patient-specific atherosclerotic carotid artery bifurcations with MRI and computational fluid dynamics modeling. Comput Biol Med 2020; 125:104015. [DOI: 10.1016/j.compbiomed.2020.104015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 09/17/2020] [Accepted: 09/17/2020] [Indexed: 12/29/2022]
|
|
24
|
Chen WL, Chuang HS. Trace Biomolecule Detection with Functionalized Janus Particles by Rotational Diffusion. Anal Chem 2020; 92:12996-13003. [PMID: 32933244 DOI: 10.1021/acs.analchem.0c01733] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Cytokines are small proteins secreted by cells in innate and adaptive immune systems. Abnormal cytokine secretion is often regarded as an early cue of dysregulation of homeostasis due to diseases or infections. Early detection allows early medical intervention. In this study, a natural phenomenon called rotational Brownian motion was characterized by Janus particles and its potential use in detection of trace biomolecules explored. Through the functionalization of the Janus particles with an antibody, the target cytokine, that is, tumor necrosis factor-α, was measured in terms of rotational diffusion. Rotational diffusion is highly sensitive to the particle volume change according to the Stokes-Einstein-Debye relation and can be quantified by blinking signal. Accordingly, 1 μm half-gold and half-fluorescent microbeads were conjugated with 200 nm nanobeads through sandwiched immunocomplexes. The light source, lead time for stabilization, and purification were investigated for optimization. Particle images can be captured with green light at 5 Hz within 300 s. Under such conditions, the functionalized Janus particles eventually achieved a limit of detection of 1 pg/mL. The rotational diffusometry realized by Janus particles was power-free and feasible for ultrasensitive detection, such as early disease detection.
Collapse
Affiliation(s)
- Wei-Long Chen
- Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan
| | - Han-Sheng Chuang
- Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan.,Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan
| |
Collapse
|
|
25
|
Nikitin PV, Ryzhova MV, Galstyan SA, Kim DS, Zubova IV, Khokhlova EA, Shugay SV. Identification of different cell clusters in the endothelium of atherosclerotic vessels and determination of inter-cluster gradient of proliferative and inflammatory activity as new diagnostic markers. Biotech Histochem 2020; 96:487-497. [PMID: 32938242 DOI: 10.1080/10520295.2020.1823016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022] Open
Abstract
To characterize atherogenesis functionally, we studied the functional heterogeneity of endotheliocytes in carotid vessels with atherosclerotic plaques and identified several distinct cell clusters. We measured the Ki-67 labeling index (Ki-67 LI), percentage of Bcl-2 cells (CP) and expression of CCL5, IL 6 and VCAM1 in each cell cluster. We also investigated how these indicators change when the plaque becomes unstable and how they affect the risk of adverse cerebrovascular events in patients. We evaluated the inter-cluster gradient of marker activity and its relation to patient prognosis. We identified five endothelial clusters: the under plaque cluster (UPC), peripheral cluster (PC), marginal cluster (MC), transient cluster (TC) and outside plaque cluster (OC). The UPC exhibited the greatest proliferative, proinflammatory and adhesive activity, but low anti-apoptotic activity. The PC exhibited the second greatest proliferative, adhesive and proinflammatory activity. Progression of atherosclerosis and transition of a stable atherosclerotic plaque to an unstable one was accompanied by increased expression of nearly all markers. The proliferative activity in the UPC, PC and OC, and the pro-inflammatory activity in UPC and anti-apoptotic activity in the PC, were correlated with prognosis. Also, two gradients of proliferative activity and a gradient of pro-inflammatory activity were associated with risk of adverse events.
Collapse
Affiliation(s)
- P V Nikitin
- P.K. Anokhin Institute of Normal Physiology, Moscow, Russian Federation
| | - M V Ryzhova
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - S A Galstyan
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - D S Kim
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - I V Zubova
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - E A Khokhlova
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| | - S V Shugay
- N. N. Burdenko National Medical Research Center of Neurosurgery, Moscow, Russian Federation
| |
Collapse
|
|
26
|
Cuevas A, Saavedra N, Salazar LA, Cavalcante MF, Silva JC, Abdalla DSP. Prodigiosin Modulates the Immune Response and Could Promote a Stable Atherosclerotic Lession in C57bl/6 Ldlr-/- Mice. Int J Mol Sci 2020; 21:ijms21176417. [PMID: 32899258 PMCID: PMC7504388 DOI: 10.3390/ijms21176417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 07/15/2020] [Accepted: 07/18/2020] [Indexed: 12/19/2022] Open
Abstract
Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.
Collapse
Affiliation(s)
- Alejandro Cuevas
- Clinical Microbiology Unit, Department of Preclinical Sciences, Faculty of Medicine, Universidad de La Frontera, Manuel Montt 112, Temuco CP 4781176, Chile
- Centro de Investigación en Medicina de Laboratorio—CeMLab, Faculty of Medicine, Universidad de La Frontera, Manuel Montt 112, Temuco CP 4781176, Chile;
- Correspondence: ; Tel.: +56-45-2744333
| | - Nicolás Saavedra
- Centro de Investigación en Medicina de Laboratorio—CeMLab, Faculty of Medicine, Universidad de La Frontera, Manuel Montt 112, Temuco CP 4781176, Chile;
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Francisco Salazar 01145, Temuco CP 4811230, Chile;
| | - Luis A. Salazar
- Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Francisco Salazar 01145, Temuco CP 4811230, Chile;
| | - Marcela F. Cavalcante
- Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo–SP 05508-000, Brazil; (M.F.C.); (J.C.S.); (D.S.P.A.)
| | - Jacqueline C. Silva
- Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo–SP 05508-000, Brazil; (M.F.C.); (J.C.S.); (D.S.P.A.)
| | - Dulcineia S. P. Abdalla
- Department of Clinical and Toxicological Analysis, Faculty of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo–SP 05508-000, Brazil; (M.F.C.); (J.C.S.); (D.S.P.A.)
| |
Collapse
|
|
27
|
Pechanova O, Dayar E, Cebova M. Therapeutic Potential of Polyphenols-Loaded Polymeric Nanoparticles in Cardiovascular System. Molecules 2020; 25:molecules25153322. [PMID: 32707934 PMCID: PMC7435870 DOI: 10.3390/molecules25153322] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/16/2020] [Accepted: 07/17/2020] [Indexed: 12/11/2022] Open
Abstract
Numerous studies document an increased production of reactive oxygen species (ROS) with a subsequent decrease in nitric oxide (NO) bioavailability in different cardiovascular diseases, including hypertension, atherosclerosis, and heart failure. Many natural polyphenols have been demonstrated to decrease ROS generation and/or to induce the endogenous antioxidant enzymatic defense system. Moreover, different polyphenolic compounds have the ability to increase the activity/expression of endothelial nitric oxide synthase (eNOS) with a subsequent enhancement of NO generation. However, as a result of low absorption and bioavailability of natural polyphenols, the beneficial effects of these substances are very limited. Recent progress in delivering polyphenols to the targeted tissues revealed new possibilities for the use of polymeric nanoparticles in increasing the efficiency and reducing the degradability of natural polyphenols. This review focuses on the effects of different natural polyphenolic substances, especially resveratrol, quercetin, curcumin, and cherry extracts, and their ability to bind to polymeric nanoparticles, and summarizes the effects of polyphenol-loaded nanoparticles, mainly in the cardiovascular system.
Collapse
|
|
28
|
Yang G, Zhang J, Jiang T, Monslow J, Tang SY, Todd L, Puré E, Chen L, FitzGerald GA. Bmal1 Deletion in Myeloid Cells Attenuates Atherosclerotic Lesion Development and Restrains Abdominal Aortic Aneurysm Formation in Hyperlipidemic Mice. Arterioscler Thromb Vasc Biol 2020; 40:1523-1532. [PMID: 32321308 PMCID: PMC7285859 DOI: 10.1161/atvbaha.120.314318] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Although the molecular components of circadian rhythms oscillate in discrete cellular components of the vasculature and many aspects of vascular function display diurnal variation, the cellular connections between the molecular clock and inflammatory cardiovascular diseases remain to be elucidated. Previously we have shown that pre- versus postnatal deletion of Bmal1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1), the nonredundant core clock gene has contrasting effects on atherogenesis. Here we investigated the effect of myeloid cell Bmal1 deletion on atherogenesis and abdominal aortic aneurysm formation in mice. Approach and Results: Mice lacking Bmal1 in myeloid cells were generated by crossing Bmal1 flox/flox mice with lysozyme 2 promoter-driven Cre recombinase mice on a hyperlipidemic low-density lipoprotein receptor-deficient background and were fed on a high-fat diet to induce atherosclerosis. Atherogenesis was restrained, concomitant with a reduction of aortic proinflammatory gene expression in myeloid cell Bmal1 knockout mice. Body weight, blood pressure, blood glucose, triglycerides, and cholesterol were unaltered. Similarly, myeloid cell depletion of Bmal1 also restrained Ang II (angiotensin II) induced formation of abdominal aortic aneurysm in hyperlipidemic mice. In vitro, RNA-Seq analysis demonstrated a proinflammatory response in cultured macrophages in which there was overexpression of Bmal1. CONCLUSIONS Myeloid cell Bmal1 deletion retards atherogenesis and restrains the formation of abdominal aortic aneurysm and may represent a potential therapeutic target for inflammatory cardiovascular diseases.
Collapse
MESH Headings
- ARNTL Transcription Factors/deficiency
- ARNTL Transcription Factors/genetics
- ARNTL Transcription Factors/physiology
- Angiotensin II/pharmacology
- Animals
- Aortic Aneurysm, Abdominal/chemically induced
- Aortic Aneurysm, Abdominal/prevention & control
- Atherosclerosis/etiology
- Atherosclerosis/pathology
- Atherosclerosis/prevention & control
- Cells, Cultured
- Crosses, Genetic
- Diet, High-Fat
- Gene Deletion
- Gene Expression
- Hyperlipidemias/complications
- Hyperlipidemias/etiology
- Inflammation
- Integrases/genetics
- Macrophages, Peritoneal/chemistry
- Macrophages, Peritoneal/physiology
- Mice
- Mice, Knockout
- Muramidase/genetics
- Myeloid Cells/chemistry
- Promoter Regions, Genetic/genetics
- Receptors, LDL/deficiency
- Receptors, LDL/genetics
Collapse
Affiliation(s)
- Guangrui Yang
- School of Bioengineering, Dalian University of Technology, China, 116024
| | - Jiayang Zhang
- Advanced Institute for Medical Sciences, Dalian Medical University, China, 116044
| | - Tingting Jiang
- Advanced Institute for Medical Sciences, Dalian Medical University, China, 116044
| | - James Monslow
- The Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, PA, 19104
| | - Soon Yew Tang
- The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA, 19104
| | - Leslie Todd
- The Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, PA, 19104
| | - Ellen Puré
- The Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, PA, 19104
| | - Lihong Chen
- Advanced Institute for Medical Sciences, Dalian Medical University, China, 116044
| | - Garret A. FitzGerald
- The Institute for Translational Medicine and Therapeutics, University of Pennsylvania, PA, 19104
| |
Collapse
|
|
29
|
Zhao TC, Wang Z, Zhao TY. The important role of histone deacetylases in modulating vascular physiology and arteriosclerosis. Atherosclerosis 2020; 303:36-42. [PMID: 32535412 DOI: 10.1016/j.atherosclerosis.2020.04.020] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Revised: 04/18/2020] [Accepted: 04/29/2020] [Indexed: 12/18/2022]
Abstract
Cardiovascular diseases are the leading cause of deaths in the world. Endothelial dysfunction followed by inflammation of the vessel wall leads to atherosclerotic lesion formation that causes ischemic heart and myocardial hypertrophy, which ultimately progress into cardiac dysfunction and failure. Histone deacetylases (HDACs) have been recognized to play crucial roles in cardiovascular disease, particularly in the epigenetic regulation of gene transcription in response to a variety of stresses. The unique nature of HDAC regulation includes that HDACs form a complex co-regulatory network with other transcription factors, deacetylate histones and non-histone proteins to facilitate the regulatory mechanism of the vascular system. The selective HDAC inhibitors are considered as the most promising target in cardiovascular disease, especially for preventing cardiac hypertrophy. In this review, we discuss our present knowledge of the cellular and molecular basis of HDACs in mediating the biological function of vascular cells and related pharmacologic interventions in vascular disease.
Collapse
Affiliation(s)
- Ting C Zhao
- Department of Surgery and Plastics Surgery, Brown University, Rhode Island Hospital, Providence, RI, USA.
| | - Zhengke Wang
- Department of Surgery, Boston University Medical School, Roger Williams Medical Center, Providence, 50 Maude Street, RI, 02908, USA
| | - Tina Y Zhao
- University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| |
Collapse
|
|
30
|
Al-Sharea A, Lee MKS, Purton LE, Hawkins ED, Murphy AJ. The haematopoietic stem cell niche: a new player in cardiovascular disease? Cardiovasc Res 2020; 115:277-291. [PMID: 30590405 DOI: 10.1093/cvr/cvy308] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 12/17/2018] [Indexed: 02/06/2023] Open
Abstract
Haematopoiesis, the process of blood production, can be altered during the initiation or progression of many diseases. Cardiovascular disease (CVD) has been shown to be heavily influenced by changes to the haematopoietic system, including the types and abundance of immune cells produced. It is now well established that innate immune cells are increased in people with CVD, and the mechanisms contributing to this can be vastly different depending on the risk factors or comorbidities present. Many of these changes begin at the level of the haematopoietic stem and progenitor cells (HSPCs) that reside in the bone marrow (BM). In general, the HSPCs and downstream myeloid progenitors are expanded via increased proliferation in the setting of atherosclerotic CVD. However, HSPCs can also be encouraged to leave the BM and colonise extramedullary sites (i.e. the spleen). Within the BM, HSPCs reside in specialized microenvironments, often referred to as a niche. To date in depth studies assessing the damage or dysregulation that occurs in the BM niche in varying CVDs are scarce. In this review, we provide a general overview of the complex components and interactions within the BM niche and how they influence the function of HSPCs. Additionally, we discuss the main findings regarding changes in the HSPC niche that influence the progression of CVD. We hypothesize that understanding the influence of the BM niche in CVD will aid in delineating new pathways for therapeutic interventions.
Collapse
Affiliation(s)
- Annas Al-Sharea
- Division of Immunometabolism, Haematopoiesis and Leukocyte Biology, Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.,Department of Immunology, Monash University, Melbourne, Australia
| | - Man Kit Sam Lee
- Division of Immunometabolism, Haematopoiesis and Leukocyte Biology, Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.,Department of Immunology, Monash University, Melbourne, Australia
| | | | - Edwin D Hawkins
- Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
| | - Andrew J Murphy
- Division of Immunometabolism, Haematopoiesis and Leukocyte Biology, Baker Heart & Diabetes Institute, 75 Commercial Road, Melbourne, VIC, Australia.,Department of Immunology, Monash University, Melbourne, Australia
| |
Collapse
|
|
31
|
Suzuki H, Mikami T, Tamada T, Ukai R, Akiyama Y, Yamamura A, Houkin K, Mikuni N. Inflammation promotes progression of thrombi in intracranial thrombotic aneurysms. Neurosurg Rev 2019; 43:1565-1573. [PMID: 31686254 DOI: 10.1007/s10143-019-01184-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/20/2019] [Accepted: 09/12/2019] [Indexed: 01/23/2023]
Abstract
Advances in the understanding of the pathogenesis of arteriosclerosis, abdominal aorta aneurysms and dissections, and carotid artery plaques have focused on chronic inflammation. In this study, we report that inflammatory changes of thrombi contribute to the enlargement and growth of giant intracranial thrombotic aneurysms. Surgical and postmortem samples were collected from 12 cases of large or giant intracranial thrombotic aneurysms diagnosed via pathological investigations. Degeneration of the aneurysmal wall and the infiltration of inflammatory cells in the thrombi were assessed. The number of blood cells and immunohistochemical stain-positive cells was enumerated, and the inflammation and neovascularization in the thrombi were assessed. In all cases, the appearance of inflammatory cells (CD68+ cells, CD206+ cells, lymphocytes, and neutrophils) was apparent in the thrombi. The number of CD34+ cells was moderately correlated with the number of CD68+ cells, and CD34+ cells significantly and strongly correlated with the number of CD206+ cells. Based on the number of neutrophils per CD68+ cells, we classified the cases into 2 groups: a macrophage inflammation-dominant group and a neutrophilic inflammation-dominant group. The neutrophilic inflammation-dominant group had significantly more cases with previous treatments and neurological symptoms due to mass effect than the macrophage inflammation-dominant group. Chronic inflammation due to macrophages in thrombi is a fundamental mechanism in the enlargement of an intracranial thrombotic aneurysm, and neutrophilic inflammation can accelerate this process. Microvascularization in thrombi is linked to inflammation and might promote thickening of the intima and repeated intimal microbleeds.
Collapse
Affiliation(s)
- Hime Suzuki
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Takeshi Mikami
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan.
| | - Tomoaki Tamada
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Ryo Ukai
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Yukinori Akiyama
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Akinori Yamamura
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| | - Kiyohiro Houkin
- Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
| | - Nobuhiro Mikuni
- Department of Neurosurgery, Sapporo Medical University, Sapporo, Hokkaido, Japan
| |
Collapse
|
|
32
|
Xu Y, Wang M, Xie Y, Jiang Y, Liu M, Yu S, Wang B, Liu Q. Activation of GPR39 with the agonist TC-G 1008 ameliorates ox-LDL-induced attachment of monocytes to endothelial cells. Eur J Pharmacol 2019; 858:172451. [PMID: 31202806 DOI: 10.1016/j.ejphar.2019.172451] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Revised: 06/09/2019] [Accepted: 06/12/2019] [Indexed: 12/24/2022]
Abstract
Attachment of monocytes to endothelial cells is a major event in the pathogenesis of atherosclerosis and cardiovascular disease. As atherosclerosis is considered to be an inflammatory disease, increased expression of proinflammatory cytokines greatly contributes to endothelial dysfunction and atherogenesis. Additionally, attachment of monocytes to endothelial cells triggered by cellular adhesion molecules such as vascular cellular adhesion molecule 1 (VCAM-1) and E-selectin plays a vital role in the development of atherosclerotic plaques. Zinc therapy has been suggested as a potential strategy for countering atherosclerosis. In the present study, for the first time to our knowledge, we investigated the potential role of the GPR39 zinc-sensing receptor in mediating the adhesion of monocytes to endothelial cells, oxidative stress and inflammation in human aortic endothelial cells induced by oxidized low-density lipoprotein (ox-LDL). Our findings show that agonism of GPR39 by the selective agonist TC-G 1008 potently reversed the effects of ox-LDL including increased expression of proinflammatory cytokines and chemokines, markers of oxidative stress, and enhanced expression of cellular adhesion molecules. Importantly, we also show that this protective effect is mediated through the nuclear factor-κB (NF-κB) pathway. Taken together, our findings suggest a potential role of GPR39 as a novel therapeutic target for the treatment and prevention of atherosclerosis induced by ox-LDL.
Collapse
Affiliation(s)
- Yiguan Xu
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Mingliang Wang
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Yun Xie
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Yumei Jiang
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Min Liu
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Shushu Yu
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Bo Wang
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China
| | - Qiliang Liu
- Department of Cardiology, Putuo People's Hospital Affiliated to Tongji University, Shanghai, 200060, China.
| |
Collapse
|
|
33
|
|
|
34
|
Dai Z, Lyu W, Xiang X, Tang Y, Hu B, Ou S, Zeng X. Immunomodulatory Effects of Enzymatic-Synthesized α-Galactooligosaccharides and Evaluation of the Structure-Activity Relationship. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:9070-9079. [PMID: 30086236 DOI: 10.1021/acs.jafc.8b01939] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
In this study, α-galactooligosaccharides (α-GOSs) were synthesized using galactose as the substrate and α-galactosidase from Aspergillus niger as the catalyst. In the reaction, synthesized products of U1, U2, U3, and U4 were detected by high-performance liquid chromatography. By mass spectrometry, nuclear magnetic resonance, and 1-phenyl-3-methyl-5-pyrazolone derivatization, U1 was the mixture of disaccharides of α-d-Gal p-(1→1)-α-d-Gal, α-d-Gal p-(1→2)-α-d-Gal, α-d-Gal p-(1→3)-α-d-Gal, α-d-Gal p-(1→4)-α-d-Gal, U2 was identified to be α-d-Gal p-(1→6)-α-d-Gal, U3 was the mixture of galactotrisaccharides linked by one α-(1→6)-glycosidic linkage and one other α-glycosidic linkage, and U4 was identified as α-d-Gal p-(1→6)-α-d-Gal p-(1→6)-α-d-Gal. Afterward, the synthesized α-GOSs (U1, U2, U3, U4, and their mixture) as well as α-GOSs (manninotriose, stachyose, ciceritol, and verbascose) obtained from natural materials were used as subjects to evaluate their immunomodulatory effects in vitro by culturing mouse macrophage RAW264.7 cells. The results showed that α-GOS with a higher degree of polymerization had better immunomodulatory activity, while to a certain extent, α-GOS linked with α-(1→6)-galactosidic linkage showed a better immunomodulatory effect.
Collapse
Affiliation(s)
- Zhuqing Dai
- College of Food Science and Technology , Nanjing Agricultural University , Nanjing , Jiangsu 210095 , People's Republic of China
- Institute of Farm Product Processing , Jiangsu Academy of Agricultural Sciences , Nanjing , Jiangsu 210014 , People's Republic of China
| | - Wanyong Lyu
- Nutrition and Food Branch of China Association of Gerontology and Geriatrics , Beijing 100050 , People's Republic of China
| | - Xiaoli Xiang
- College of Food Science and Technology , Nanjing Agricultural University , Nanjing , Jiangsu 210095 , People's Republic of China
| | - Yuhong Tang
- College of Food Science and Technology , Nanjing Agricultural University , Nanjing , Jiangsu 210095 , People's Republic of China
| | - Bing Hu
- College of Food Science and Technology , Nanjing Agricultural University , Nanjing , Jiangsu 210095 , People's Republic of China
| | - Shiyi Ou
- Department of Food Science and Engineering , Jinan University , Guangzhou , Guangdong 510632 , People's Republic of China
| | - Xiaoxiong Zeng
- College of Food Science and Technology , Nanjing Agricultural University , Nanjing , Jiangsu 210095 , People's Republic of China
| |
Collapse
|
|
35
|
Pu-erh Tea Ameliorates Atherosclerosis Associated with Promoting Macrophage Apoptosis by Reducing NF- κB Activation in ApoE Knockout Mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:3197829. [PMID: 30210650 PMCID: PMC6126088 DOI: 10.1155/2018/3197829] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Revised: 05/06/2018] [Accepted: 05/20/2018] [Indexed: 11/20/2022]
Abstract
We explored whether pu-erh tea consumption ameliorates atherosclerosis and the possible mechanism for its effects in apolipoprotein E-deficient (ApoE−/−) mice. Our data showed that pu-erh tea consumption markedly reduced early fatty streak formation and the advanced fibrofatty plaque sizes. Additionally, the mean proportion of inflammatory macrophages in the plaque decreased, and the number of apoptotic macrophages increased significantly. NF-κB activity in peritoneal macrophages decreased by 75.6% compared to the controls, similar with the levels of IL-6, IL-12, and TNF-α expression. The tea extract increased the apoptosis of RAW264.7 cells by decreasing NF-κB activation and reducing the inflammatory cytokine expression. In conclusion, pu-erh tea ameliorates atherosclerosis progress by alleviating the chronic inflammatory state by reducing NF-κB activation and promoting macrophage apoptosis in atherosclerotic plaques.
Collapse
|
|
36
|
Lewandowska H, Stępkowski TM, Męczyńska-Wielgosz S, Sikorska K, Sadło J, Dudek J, Kruszewski M. LDL dinitrosyl iron complex acts as an iron donor in mouse macrophages. J Inorg Biochem 2018; 188:29-37. [PMID: 30119015 DOI: 10.1016/j.jinorgbio.2018.08.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 07/22/2018] [Accepted: 08/02/2018] [Indexed: 12/27/2022]
Abstract
[Fe(NO)2] - modified nanoparticles of low-density protein (DNICLDL) can serve as conveyors of iron in the form of stable complexes with ApoB100 protein. As reported recently, in human hepatoma cells DNICLDL significantly increased the total iron content, while showing low toxicity. In the present work, we focused on the effects of internalization of DNIC-modified lipoproteins in macrophages, with special regards to cytotoxicity. DNICLDL was administered to a model macrophage cell line, RAW 264.7. Administration of DNICLDL considerably increased total iron content. High increase of iron was accompanied by moderate toxicity. As shown by in vitro plasmid nicking assay, chelation of iron in the form of DNIC strongly reduced the iron-related reactive oxygen species (ROS) -induced DNA damage. In addition, DNICLDL, plausibly due to its NO-donating activity, did not induce inducible nitric oxide synthase (iNOS) expression, as opposed to other forms of low-density protein (LDL).
Collapse
Affiliation(s)
- Hanna Lewandowska
- Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland.
| | - Tomasz M Stępkowski
- Laboratory of Mitochondrial Biogenesis, Centre of New Technologies UW, Banacha 2c, 02-097 Warsaw, Poland
| | | | - Katarzyna Sikorska
- Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland
| | - Jarosław Sadło
- Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland
| | - Jakub Dudek
- Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland
| | - Marcin Kruszewski
- Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland; Faculty of Medicine, University of Information Technology and Management in Rzeszów, ul. Sucharskiego 2, 35-225 Rzeszów, Poland; Department of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland
| |
Collapse
|
|
37
|
Tulamo R, Frösen J, Hernesniemi J, Niemelä M. Inflammatory changes in the aneurysm wall: a review. J Neurointerv Surg 2018; 10:i58-i67. [DOI: 10.1136/jnis.2009.002055.rep] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 12/17/2009] [Accepted: 12/18/2009] [Indexed: 02/06/2023]
Abstract
Rupture of a saccular intracranial artery aneurysm (IA) causes subarachnoid hemorrhage, a significant cause of stroke and death. The current treatment options, endovascular coiling and clipping, are invasive and somewhat risky. Since only some IAs rupture, those IAs at risk for rupture should be identified. However, to improve the imaging of rupture-prone IAs and improve IA treatment, IA wall pathobiology requires more thorough knowledge. Chronic inflammation has become understood as an important phenomenon in IA wall pathobiology, featuring inflammatory cell infiltration as well as proliferative and fibrotic remodulatory responses. We review the literature on what is known about inflammation in the IA wall and also review the probable mechanisms of how inflammation would result in the degenerative changes that ultimately lead to IA wall rupture. We also discuss current options in imaging inflammation and how knowledge of inflammation in IA walls may improve IA treatment.
Collapse
|
|
38
|
Wang SH, Yu TY, Tsai FC, Weston CJ, Lin MS, Hung CS, Kao HL, Li YI, Solé M, Unzeta M, Chen YL, Chuang LM, Li HY. Inhibition of semicarbazide-sensitive amine oxidase reduces atherosclerosis in apolipoprotein E-deficient mice. Transl Res 2018; 197:12-31. [PMID: 29653075 DOI: 10.1016/j.trsl.2018.03.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2017] [Revised: 02/28/2018] [Accepted: 03/18/2018] [Indexed: 01/08/2023]
Abstract
Inflammation, oxidative stress, and formation of advanced glycated end products (AGEs) and advanced lipoxidation end products (ALEs) are important for atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation and has semicarbazide-sensitive amine oxidase (SSAO) activity, which catalyzes oxidative deamination to produce hydrogen peroxide and aldehydes, leading to generation of AGEs and ALEs. However, the effect of VAP-1/SSAO inhibition on atherosclerosis remains controversial, and no studies used coronary angiography to evaluate if plasma VAP-1/SSAO is a biomarker for coronary artery disease (CAD). Here, we examined if plasma VAP-1/SSAO is a biomarker for CAD diagnosed by coronary angiography in humans and investigated the effect of VAP-1/SSAO inhibition by a specific inhibitor PXS-4728A on atherosclerosis in cell and animal models. In the study, VAP-1/SSAO expression was increased in plaques in humans and in apolipoprotein E (ApoE)-deficient mice, and colocalized with vascular endothelial cells and smooth muscle cells (SMCs). Patients with CAD had higher plasma VAP-1/SSAO than those without CAD. Plasma VAP-1/SSAO was positively associated with the extent of CAD. In ApoE-deficient mice, VAP-1/SSAO inhibition reduced atheroma and decreased oxidative stress. VAP-1/SSAO inhibition attenuated the expression of adhesion molecules, chemoattractant proteins, and proinflammatory cytokines in the aorta, and suppressed monocyte adhesion and transmigration across human umbilical vein endothelial cells. Consequently, the expression of markers for macrophage recruitment and activation in plaques was decreased by VAP-1/SSAO inhibition. Besides, VAP-1/SSAO inhibition suppressed proliferation and migration of A7r5 SMC. Our data suggest that plasma VAP-1/SSAO is a novel biomarker for the presence and the extent of CAD in humans. VAP-1/SSAO inhibition by PXS-4728A is a potential treatment for atherosclerosis.
Collapse
Affiliation(s)
- Shu-Huei Wang
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tse-Ya Yu
- Health Management Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Feng-Chiao Tsai
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chris J Weston
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Mao-Shin Lin
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Sheng Hung
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsien-Li Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yu-I Li
- Department and Graduate Institute of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Montse Solé
- Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona (UAB), Bellaterra (Barcelona), Spain
| | - Mercedes Unzeta
- Institut de Neurociències i Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona (UAB), Bellaterra (Barcelona), Spain
| | - Yuh-Lien Chen
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Lee-Ming Chuang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Yuan Li
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
| |
Collapse
|
|
39
|
Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits. Sci Rep 2018; 8:9249. [PMID: 29915377 PMCID: PMC6006253 DOI: 10.1038/s41598-018-27551-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 06/05/2018] [Indexed: 01/05/2023] Open
Abstract
Inflammation, oxidative stress, and the formation of advanced glycated end-products (AGEs) are important components of atherosclerosis. Vascular adhesion protein-1 (VAP-1) participates in inflammation. Its enzymatic activity, semicarbazide-sensitive amine oxidase (SSAO), can catalyze oxidative deamination reactions to produce hydrogen peroxide and aldehydes, leading to the subsequent generation of AGEs. This study aimed to investigate the effect of VAP-1/SSAO inhibition on atherosclerosis. In our study, immunohistochemical staining showed that atherosclerotic plaques displayed higher VAP-1 expression than normal arterial walls in apolipoprotein E-deficient mice, cholesterol-fed New Zealand White rabbits and humans. In cholesterol-fed rabbits, VAP-1 was expressed on endothelial cells and smooth muscle cells in the thickened intima of the aorta. Treatment with PXS-4728A, a selective VAP-1/SSAO inhibitor, in cholesterol-fed rabbits significantly decreased SSAO-specific hydrogen peroxide generation in the aorta and reduced atherosclerotic plaques. VAP-1/SSAO inhibition also lowered blood low-density lipoprotein cholesterol, reduced the expression of adhesion molecules and inflammatory cytokines, suppressed recruitment and activation of macrophages, and decreased migration and proliferation of SMC. In conclusion, VAP-1/SSAO inhibition reduces atherosclerosis and may act through suppression of several important mechanisms for atherosclerosis.
Collapse
|
|
40
|
Nakamura M. Histological and immunological characteristics of the junctional epithelium. JAPANESE DENTAL SCIENCE REVIEW 2018; 54:59-65. [PMID: 29755616 PMCID: PMC5944073 DOI: 10.1016/j.jdsr.2017.11.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Revised: 10/23/2017] [Accepted: 11/14/2017] [Indexed: 01/08/2023] Open
Abstract
The continuity of epithelial tissue is collapsed by tooth eruption. The junctional epithelium (JE) is attached to the tooth surface by hemidesmosomes, which constitutes the front-line defense against periodontal bacterial infection. JE constitutively expresses intercellular adhesion molecule-1 (ICAM-1), and neutrophils and lymphocytes penetrate into JE via interaction between ICAM-1 and LFA-1 expressed on the surface of these migrating cells. JE also expresses cytokines and chemokines. These functions of JE are maintained even in germ-free condition. Therefore, the constitutive expression of adhesion molecules, cytokines, and chemokines might be used not only for anti-pathogenic defense but also for maintaining the physiological homeostasis of JE. In this review, we have mainly focused on the structural and functional features of JE, and discussed the function of intraepithelial lymphocytes in JE as a front-line anti-microbial defense barrier and regulator of JE hemostasis.
Collapse
Affiliation(s)
- Masanori Nakamura
- Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| |
Collapse
|
|
41
|
Nam HS, Kang WJ, Lee MW, Song JW, Kim JW, Oh WY, Yoo H. Multispectral analog-mean-delay fluorescence lifetime imaging combined with optical coherence tomography. BIOMEDICAL OPTICS EXPRESS 2018; 9:1930-1947. [PMID: 29675330 PMCID: PMC5905935 DOI: 10.1364/boe.9.001930] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 03/15/2018] [Accepted: 03/18/2018] [Indexed: 05/19/2023]
Abstract
The pathophysiological progression of chronic diseases, including atherosclerosis and cancer, is closely related to compositional changes in biological tissues containing endogenous fluorophores such as collagen, elastin, and NADH, which exhibit strong autofluorescence under ultraviolet excitation. Fluorescence lifetime imaging (FLIm) provides robust detection of the compositional changes by measuring fluorescence lifetime, which is an inherent property of a fluorophore. In this paper, we present a dual-modality system combining a multispectral analog-mean-delay (AMD) FLIm and a high-speed swept-source optical coherence tomography (OCT) to simultaneously visualize the cross-sectional morphology and biochemical compositional information of a biological tissue. Experiments using standard fluorescent solutions showed that the fluorescence lifetime could be measured with a precision of less than 40 psec using the multispectral AMD-FLIm without averaging. In addition, we performed ex vivo imaging on rabbit iliac normal-looking and atherosclerotic specimens to demonstrate the feasibility of the combined FLIm-OCT system for atherosclerosis imaging. We expect that the combined FLIm-OCT will be a promising next-generation imaging technique for diagnosing atherosclerosis and cancer due to the advantages of the proposed label-free high-precision multispectral lifetime measurement.
Collapse
Affiliation(s)
- Hyeong Soo Nam
- Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04673, South Korea
- Equally contributed to this study
| | - Woo Jae Kang
- Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Gwahang-no, Yuseong-gu, Daejeon 34141, South Korea
- Equally contributed to this study
| | - Min Woo Lee
- Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04673, South Korea
| | - Joon Woo Song
- Cardiovascular Center, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, South Korea
| | - Jin Won Kim
- Cardiovascular Center, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, South Korea
| | - Wang-Yuhl Oh
- Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, 291 Gwahang-no, Yuseong-gu, Daejeon 34141, South Korea
| | - Hongki Yoo
- Department of Biomedical Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04673, South Korea
| |
Collapse
|
|
42
|
Saha AK, Mousavi M, Dallo SF, Evani SJ, Ramasubramanian AK. Influence of membrane cholesterol on monocyte chemotaxis. Cell Immunol 2017; 324:74-77. [PMID: 29241586 DOI: 10.1016/j.cellimm.2017.12.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 10/13/2017] [Accepted: 12/08/2017] [Indexed: 11/28/2022]
Abstract
Cholesterol content influences several important physiological functions due to its effect on membrane receptors. In this work, we tested the hypothesis that cellular cholesterol alters chemotactic response of monocytes to Monocyte Chemoattractant Protein-1 (MCP-1) due to their effect on the receptor, CCR2. We used Methyl-β-cyclodextrin (MβCD) to alter the baseline cholesterol in human monocytic cell line THP-1, and evaluated their chemotactic response to MCP-1. Compared to untreated cells, cholesterol enrichment increased the number of monocytes transmigrated in response to MCP-1 while depletion had opposite effect. Using imaging flow cytometry, we established that these differences were due to alterations in expression levels, but not the surface distribution, of CCR2.
Collapse
Affiliation(s)
- Amit K Saha
- Department of Biomedical, Chemical and Materials Engineering, San José State University, San José, CA 95192, USA
| | - Marzieh Mousavi
- Department of Biomedical, Chemical and Materials Engineering, San José State University, San José, CA 95192, USA
| | - Shatha F Dallo
- Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Shankar J Evani
- Department of Biomedical Engineering, The University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Anand K Ramasubramanian
- Department of Biomedical, Chemical and Materials Engineering, San José State University, San José, CA 95192, USA.
| |
Collapse
|
|
43
|
Plant-Based Nutrition: An Essential Component of Cardiovascular Disease Prevention and Management. Curr Cardiol Rep 2017; 19:104. [DOI: 10.1007/s11886-017-0909-z] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
|
|
44
|
Grell AS, Frederiksen SD, Edvinsson L, Ansar S. Cerebrovascular gene expression in spontaneously hypertensive rats. PLoS One 2017; 12:e0184233. [PMID: 28880918 PMCID: PMC5589213 DOI: 10.1371/journal.pone.0184233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Accepted: 08/21/2017] [Indexed: 11/22/2022] Open
Abstract
Hypertension is a hemodynamic disorder and one of the most important and well-established risk factors for vascular diseases such as stroke. Blood vessels exposed to chronic shear stress develop structural changes and remodeling of the vascular wall through many complex mechanisms. However, the molecular mechanisms involved are not fully understood. Hypertension-susceptible genes may provide a novel insight into potential molecular mechanisms of hypertension and secondary complications associated with hypertension. The aim of this exploratory study was to identify gene expression differences in the middle cerebral arteries between 12-week-old male spontaneously hypertensive rats and their normotensive Wistar-Kyoto rats using an Affymetrix whole-transcriptome expression profiling. Quantitative PCR and western blotting were used to verify genes of interest. 169 genes were differentially expressed in the middle cerebral arteries from hypertensive compared to normotensive rats. The gene expression of 72 genes was decreased and the gene expression of 97 genes was increased. The following genes with a fold difference ≥1.40 were verified by quantitative PCR; Postn, Olr1, Fas, Vldlr, Mmp2, Timp1, Serpine1, Mmp11, Cd34, Ptgs1 and Ptgs2. The gene expression of Postn, Olr1, Fas, Vldlr, Mmp2, Timp1 and Serpine1 and the protein expression of LOX1 (also known as OLR1) were significantly increased in the middle cerebral arteries from spontaneously hypertensive rats compared to Wistar-Kyoto rats. In conclusion, the identified genes in the middle cerebral arteries from spontaneously hypertensive rats could be possible mediators of the vascular changes and secondary complications associated with hypertension. This study supports the selection of key genes to investigate in the future research of hypertension-induced end-organ damage.
Collapse
Affiliation(s)
- Anne-Sofie Grell
- Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, Glostrup, Denmark
- * E-mail:
| | - Simona Denise Frederiksen
- Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, Glostrup, Denmark
| | - Lars Edvinsson
- Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet Glostrup, Glostrup, Denmark
- Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden
| | - Saema Ansar
- Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Lund, Sweden
| |
Collapse
|
|
45
|
Savastano LE, Seibel EJ. Scanning Fiber Angioscopy: A Multimodal Intravascular Imaging Platform for Carotid Atherosclerosis. Neurosurgery 2017; 64:188-198. [PMID: 28899060 DOI: 10.1093/neuros/nyx322] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Accepted: 08/01/2017] [Indexed: 01/28/2023] Open
Affiliation(s)
- Luis E Savastano
- Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan
| | - Eric J Seibel
- Department of Mechanical Engineering, University of Washington, Seattle, Washington
| |
Collapse
|
|
46
|
König S, Schlereth T, Birklein F. Molecular signature of complex regional pain syndrome (CRPS) and its analysis. Expert Rev Proteomics 2017; 14:857-867. [PMID: 28803495 DOI: 10.1080/14789450.2017.1366859] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Simone König
- Core Unit Proteomics, Interdisciplinary Center for Clinical Research, University of Münster, Münster, Germany
| | | | | |
Collapse
|
|
47
|
Ji Q, Meng K, Yu K, Huang S, Huang Y, Min X, Zhong Y, Wu B, Liu Y, Nie S, Zhang J, Zhou Y, Zeng Q. Exogenous interleukin 37 ameliorates atherosclerosis via inducing the Treg response in ApoE-deficient mice. Sci Rep 2017; 7:3310. [PMID: 28607385 PMCID: PMC5468328 DOI: 10.1038/s41598-017-02987-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Accepted: 04/21/2017] [Indexed: 01/08/2023] Open
Abstract
Our previous study indicated that interleukin (IL)-37 is involved in atherosclerosis. In the present study, Anterior tibial arteries were collected from diabetes patients and controls. A histopathological analysis showed that IL-37 was over-expressed in human atherosclerotic plaques. Many types of cells including macrophages, vascular smooth muscle cells (VSMCs), endothelial cells and T lymphocyte expressed IL-37 in human atherosclerotic plaques. ApoE-/- mice were divided into a control group and a recombinant human IL-37-treated group. The IL-37 treatment resulted in a significant decrease in macrophages and CD4+ T lymphocytes and a substantial increase in VSMCs and collagen in atherosclerotic plaques, resulting in a reduction in atherosclerotic plaque size. Furthermore, the IL-37 treatment modulated the CD4+ T lymphocyte activity, including a decrease in T helper cell type 1 (Th1) and Th17 cells and an increase in regulatory T (Treg) cells, and inhibited the maturity of dendritic cells both in vivo and in vitro. In addition, treatment with anti-IL-10 receptor monoclonal antibody abrogated the anti-atherosclerotic effects of IL-37. These data suggest that exogenous IL-37 ameliorates atherosclerosis via inducing the Treg response. IL-37 may be a novel therapeutic to prevent and treat atherosclerotic disease.
Collapse
Affiliation(s)
- Qingwei Ji
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China
| | - Kai Meng
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kunwu Yu
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Song Huang
- Department of Orthopedics, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ying Huang
- Department of Ultrasound, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China
| | - Xiaohong Min
- Department of Pathology, Puren Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Yucheng Zhong
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bangwei Wu
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuzhou Liu
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaoping Nie
- Emergency & Critical Care Center, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China
| | - Jianwei Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China
| | - Yujie Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China.
| | - Qiutang Zeng
- Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| |
Collapse
|
|
48
|
Multimodal laser-based angioscopy for structural, chemical and biological imaging of atherosclerosis. Nat Biomed Eng 2017. [PMID: 28555172 DOI: 10.1038/s41551-016-0023.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The complex nature of atherosclerosis demands high-resolution approaches to identify subtle thrombogenic lesions and define the risk of plaque rupture. Here, we report the proof-of-concept use of a multimodal scanning fiber endoscope (SFE) consisting of a single optical fiber scanned by a piezoelectric drive that illuminates tissue with red, blue, and green laser beams, and digitally reconstructs images at 30 Hz with high resolution and large fields-of-view. By combining laser-induced reflectance and fluorescence emission of intrinsic fluorescent constituents in arterial tissues, the SFE allowed us to co-generate endoscopic videos with a label-free biochemical map to derive a morphological and spectral classifier capable of discriminating early, intermediate, advanced, and complicated atherosclerotic plaques. We demonstrate the capability of scanning fiber angioscopy for the molecular imaging of vulnerable atherosclerosis by targeting proteolytic activity with a fluorescent probe activated by matrix metalloproteinases. We also show that the SFE generates high-quality spectral images in vivo in an animal model with medium-sized arteries. Multimodal laser-based angioscopy could become a platform for the diagnosis, prognosis, and image-guided therapy of atherosclerosis.
Collapse
|
|
49
|
Park JB. N-Caffeoyltryptamine, a Potent Anti-Inflammatory Phenolic Amide, Suppressed MCP-1 Expression in LPS-stimulated THP-1 Cells and Rats Fed a High-Fat Diet. Int J Mol Sci 2017; 18:E1148. [PMID: 28555020 PMCID: PMC5485972 DOI: 10.3390/ijms18061148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2017] [Revised: 05/22/2017] [Accepted: 05/24/2017] [Indexed: 12/20/2022] Open
Abstract
Monocyte chemoattractant protein-1 (MCP-1) is a well-known chemokine critically involved in the pathophysiological progression of several inflammatory diseases including arthrosclerosis. N-caffeoyltryptamine is a phenolic amide with strong anti-inflammatory effects. Therefore, in this paper, the potential effect of N-caffeoyltryptamine on MCP-1 expression was investigated as a potential p38 mitogen-activated protein (MAP) kinase inhibitor in vitro and in vivo. At the concentration of 20 μM, N-caffeoyltryptamine significantly inhibited p38 MAP kinase α, β, γ and δ by 15-50% (p < 0.05), particularly p38 MAP kinase α (IC50 = 16.7 μM) and β (IC50 = 18.3 μM). Also, the pretreatment of the lipopolysaccharide (LPS)-stimulated THP-1 cells with N-caffeoyltryptamine (10, 20 and 40 μM) led to significant suppression of MCP-1 production by 10-45% (p < 0.05) in the cells. Additionally, N-caffeoyltryptamine was also able to significantly downregulate MCP-1 mRNA expression in the THP-1 cells (p < 0.05). On the basis of this strong inhibition in vitro, an animal study was conducted to confirm this inhibitory effect in vivo. Rats were divided into three groups (n = 8): a normal control diet (C), a high-fat diet (HF), or a high-fat diet supplemented with N-caffeoyltryptamine (2 mg per day) (HFS). After 16 weeks, blood samples were collected from the rats in each group, and MCP-1 levels were determined in plasma with other atherogenic markers (C-reactive protein and soluble E-selectin (sE-selectin)). As expected, the average MCP-1 levels of the HF group were found to be higher than those of the C group (p < 0.05). However, the MCP-1 levels of the HFS group were significantly lower than those of the HF group (p < 0.05), suggesting that N-caffeoyltryptamine could decrease MCP-1 expression in vivo. Related to other atherogenic markers such as C-reactive protein and sE-selectin, there was no significant difference in their levels between the HF and HFS groups. These data suggest that N-caffeoyltryptamine may specifically suppress MCP-1 expression in vitro and in vivo, possibly by inhibiting p38 MAP kinase.
Collapse
Affiliation(s)
- Jae B Park
- Diet, Genomics, and Immunology Laboratory, Beltsville Human Nutrition Research Center, The Agricultural Research Service, The United States Department of Agriculture, Bldg. 307C, Rm. 131, Beltsville, MD 20705, USA.
| |
Collapse
|
|
50
|
Zhuang X, Wu B, Li J, Shi H, Jin B, Luo X. The emerging role of interleukin-37 in cardiovascular diseases. IMMUNITY INFLAMMATION AND DISEASE 2017; 5:373-379. [PMID: 28548248 PMCID: PMC5569376 DOI: 10.1002/iid3.159] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Accepted: 02/09/2017] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Interleukin (IL)-37 is a newly identified member of the IL-1 family, and shows a growing role in a variety of diseases. This review aims at summarizing and discussing the role of IL-37 in cardiovascular diseases. METHODS Data for this review were identified by searches of MEDLINE, Embase, and PubMed using appropriate search terms. RESULTS IL-37 is a newly identified cytokine belonging to the IL-1 family and is expressed in inflammatory immune cells and several parenchymal cells. It has potent anti-inflammatory and immunosuppressive properties, with two mechanisms underlying this function. IL-37 is produced as a precursor and then cleaved into mature form in the cytoplasm by caspase-1, translocating to nucleus and suppressing the transcription of several pro-inflammatory genes by binding SMAD-3. Besides, IL-37 can be secreted extracellularly, and binds to IL-18Ra chain and recruits Toll/IL-1R (TIR)-8 for transducing anti-inflammatory signaling. IL-37 is upregulated in an inducible manner and negatively regulates signaling mediated by TLR agonists and pro-inflammatory cytokines. The cytokine has been shown to inhibit both innate and adaptive immunological responses, exert antitumor effects, and act as a prognostic marker in a variety of autoimmune diseases. CONCLUSIONS Recent studies have suggested that IL-37 plays a role in cardiovascular diseases. In this review, we provide an overview of the cytokine biology, discuss recent advances made in unraveling its cardio-protective effects, and suggest guidelines for future research.
Collapse
Affiliation(s)
- Xinyu Zhuang
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| | - Bangwei Wu
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| | - Jian Li
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| | - Haiming Shi
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| | - Bo Jin
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| | - Xinping Luo
- Department of CardiologyHuashan HospitalFudan UniversityShanghaiChina
| |
Collapse
|