|
1
|
Shah JT, Shah KT, Mandal S, Garshick MS, Femia AN. Nonsteroidal immune-modulating therapies and reduced risk of adverse cardiovascular events in dermatomyositis and polymyositis: A cohort study in the All of Us research program. J Am Acad Dermatol 2025; 92:875-878. [PMID: 39547326 DOI: 10.1016/j.jaad.2024.10.075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/01/2024] [Accepted: 10/21/2024] [Indexed: 11/17/2024]
Affiliation(s)
- Jill T Shah
- Ronald O. Perelman Department of Dermatology, New York University Langone Health, New York, New York
| | - Keya T Shah
- Department of Medicine, NYU Langone Long Island Hospital, Mineola, New York
| | - Soutrik Mandal
- Department of Population Health, NYU Grossman School of Medicine, New York, New York
| | - Michael S Garshick
- Ronald O. Perelman Department of Dermatology, New York University Langone Health, New York, New York; Leon H. Charney Division of Cardiology, Department of Medicine, New York University Langone Health, New York, New York
| | - Alisa N Femia
- Ronald O. Perelman Department of Dermatology, New York University Langone Health, New York, New York.
| |
Collapse
|
|
2
|
Bartoloni E, Cacciapaglia F, Erre GL, Gremese E, Manfredi A, Piga M, Sakellariou G, Spinelli FR, Viapiana O, Atzeni F. Immunomodulation for accelerated atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Autoimmun Rev 2025; 24:103760. [PMID: 39894242 DOI: 10.1016/j.autrev.2025.103760] [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: 05/18/2024] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/04/2025]
Abstract
In the last decades, consisting evidence supported a close relationship between both innate and adaptive immune systems and the accelerated cardiovascular (CV) disease characterizing autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Indeed, several cell lines involved in the pathogenesis of these autoimmune diseases, such as macrophages and dendritic cells, as well as different T and B lymphocyte subsets, and inflammatory cytokines, have been demonstrated to be directly involved in the mechanisms underlying early atherosclerotic arterial wall damage. Traditional CV risk factors play a concomitant role but do not sufficiently account for the increased prevalence of CV disease in these patients. Indeed, the pathophysiological link between RA and SLE and atherosclerosis is based on complex inflammatory pathways that interconnect these conditions and may explain the significant morbidity and mortality rates demonstrated in these patients, with consequent significant negative effects on quality of life and long-term survival. Consequently, it is intriguing to hypothesize that immunosuppressive drugs commonly used in the treatment of these pathologies may also exert an immunomodulatory and anti-inflammatory effect in mitigating the atherosclerotic damage that has been demonstrated to occur early in the initial stages of the disease. Recognizing risk factors, predicting occurrences and early intervention to prevent CV disease development have emerged as critical objectives in RA and SLE treatment. In this review, we aimed to provide an updated overview of the atherogenic effects exerted by the immune and inflammatory pathways involved in the pathogenesis of RA and SLE. Moreover, we examined the available evidence which may support the potential effects of immunosuppressive therapies in reducing CV damage and, consequently, CV disease risk in these patients.
Collapse
Affiliation(s)
- Elena Bartoloni
- Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, Italy
| | - Fabio Cacciapaglia
- Rheumatology Unit, Department of Precision and Regenerative Medicine and Ionian Area (DePReMeI), University of Bari, Bari, Italy; Department of Medicine and Surgery, LUM University "Giuseppe De Gennaro" Casamassima & Rheumatology Service "Miulli" General Hospital Acquaviva delle Fonti, Bari, Italy
| | - Gian Luca Erre
- Dipartimento di Scienze Mediche, Chirurgiche e Sperimentali, Università degli Studi di Sassari, Italy
| | - Elisa Gremese
- Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Andreina Manfredi
- University of Modena and Reggio Emilia,AUSL-IRCCS Reggio Emilia, Reggio Emilia, Italy
| | - Matteo Piga
- Rheumatology Unit, AOU Cagliari, Department of Medical Sciences and Public Health, University of Cagliari, Italy
| | - Garifallia Sakellariou
- Department of Internal Medicine and Therapeutics, University of Pavia, Istituti Clinici Scientifici Maugeri, Pavia, Italy
| | - Francesca Romana Spinelli
- Reumatology Unit, Department of Internal, Anesthesiological, and Cardiovascular Clinical Sciences, Sapienza University of Rome, Rome, Italy
| | - Ombretta Viapiana
- Rheumatology Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Italy
| | - Fabiola Atzeni
- Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Italy.
| |
Collapse
|
|
3
|
Tasouli-Drakou V, Ogurek I, Shaikh T, Ringor M, DiCaro MV, Lei K. Atherosclerosis: A Comprehensive Review of Molecular Factors and Mechanisms. Int J Mol Sci 2025; 26:1364. [PMID: 39941130 PMCID: PMC11818631 DOI: 10.3390/ijms26031364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 01/30/2025] [Accepted: 02/01/2025] [Indexed: 02/16/2025] Open
Abstract
Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to the increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, these processes contribute further to endothelial dysfunction and plaque formation. Herein, we aim to provide insight into the molecular pathways and mechanisms implicated in the initiation and progression of atherosclerotic plaques, and to review the risk factors associated with their development.
Collapse
Affiliation(s)
- Vasiliki Tasouli-Drakou
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, NV 89106, USA; (I.O.); (T.S.); (M.R.); (M.V.D.)
| | - Ian Ogurek
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, NV 89106, USA; (I.O.); (T.S.); (M.R.); (M.V.D.)
| | - Taha Shaikh
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, NV 89106, USA; (I.O.); (T.S.); (M.R.); (M.V.D.)
| | - Marc Ringor
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, NV 89106, USA; (I.O.); (T.S.); (M.R.); (M.V.D.)
| | - Michael V. DiCaro
- Department of Internal Medicine, Kirk Kerkorian School of Medicine at the University of Nevada, Las Vegas, NV 89106, USA; (I.O.); (T.S.); (M.R.); (M.V.D.)
| | - KaChon Lei
- Department of Cardiovascular Medicine, University of Nevada, Las Vegas, NV 89106, USA;
| |
Collapse
|
|
4
|
Dong Q, Dai G, Quan N, Tong Q. Role of natural products in cardiovascular disease. Mol Cell Biochem 2025; 480:733-745. [PMID: 38879838 DOI: 10.1007/s11010-024-05048-3] [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: 04/19/2024] [Accepted: 06/09/2024] [Indexed: 01/03/2025]
Abstract
As the world's aging population increases, cardiovascular diseases (CVDs) associated with aging deserve increasing attention. CVD in association with age is considered a major cause of morbidity and mortality worldwide. In this review, we provide an overview of the key molecular pathways, cellular processes such as autophagy, oxidative stress, inflammatory responses, myocardial remodeling and ischemia-refocused injury that accompany CVD as well as the natural products of targeting these mechanisms and some of the dietary habits that have been studied in cardiovascular-related diseases. The potential preventive and therapeutic avenues resulting from these dietary habits and natural products related to animal models and clinical studies can help us to better understand the processes involved in cardiovascular diseases and provide recommendations to reduce the cardiovascular burden associated with aging heart.
Collapse
Affiliation(s)
- Qi Dong
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Gaoying Dai
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, China
| | - Nanhu Quan
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, China.
| | - Qian Tong
- Department of Cardiovascular Center, The First Hospital of Jilin University, Changchun, 130021, China.
| |
Collapse
|
|
5
|
Punda P, Kumric M, Baric Zizic A, Sladic S, Vuletic M, Supe Domic D, Vilovic M, Rusic D, Bozic J. Catestatin and Advanced Glycation End-Products: Potential Indicators of Cardiovascular Risk in Hashimoto's Thyroiditis. Biomolecules 2025; 15:169. [PMID: 40001472 PMCID: PMC11852764 DOI: 10.3390/biom15020169] [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: 10/03/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/27/2025] Open
Abstract
Accumulating evidence suggests that overt hypothyroidism is associated with accelerated atherosclerosis, thereby increasing the risk for major cardiovascular events. The present study aimed to investigate the associations between serum catestatin levels and advanced glycation end-products (AGEs), indicators of vascular health, in individuals with Hashimoto's thyroiditis compared to healthy controls. A total of 100 female patients with Hashimoto's thyroiditis and 100 age-matched healthy controls were included in the study. Serum catestatin levels (10.2 (6.5-15.8) vs. 6.4 (4.1-9.3) ng/mL, p < 0.001) and tissue levels of AGEs (2.21 ± 0.55 ng/mL vs. 1.89 ± 0.56, p < 0.001) were both significantly higher in the Hashimoto's group compared to the healthy age-matched controls. A positive correlation was observed between catestatin and AGEs in the overall population (r = 0.489, p < 0.001) and within the Hashimoto's group (r = 0.457, p < 0.001). Additionally, weak positive correlations were noted between catestatin and high-sensitivity C-reactive protein, as well as anti-thyroid peroxidase antibodies (r = 0.277, p = 0.005 and r = 0.229, p = 0.024, respectively). All of these associations were confirmed through multivariate analyses. The present analysis indicates that catestatin might be implicated in cardiovascular consequences of Hashimoto's thyroiditis. However, future research should focus on longitudinal studies to explore if the causal relationship exists.
Collapse
Affiliation(s)
- Petra Punda
- Clinical Department of Diagnostic and Interventional Radiology, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia;
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia; (M.K.); (M.V.)
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Ana Baric Zizic
- Department of Nuclear Medicine, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (A.B.Z.); (S.S.)
- Department of Nuclear Medicine, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Sanda Sladic
- Department of Nuclear Medicine, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (A.B.Z.); (S.S.)
| | - Marko Vuletic
- Department of Nuclear Medicine, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia; (A.B.Z.); (S.S.)
| | - Daniela Supe Domic
- Department of Health Studies, University of Split, Rudera Boskovica 35, 21000 Split, Croatia;
- Department of Medical Laboratory Diagnostics, University Hospital of Split, Spinciceva 1, 21000 Split, Croatia
| | - Marino Vilovic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia; (M.K.); (M.V.)
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| | - Doris Rusic
- Department of Pharmacy, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia;
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia; (M.K.); (M.V.)
- Laboratory for Cardiometabolic Research, University of Split School of Medicine, Soltanska 2A, 21000 Split, Croatia
| |
Collapse
|
|
6
|
Gu M, Xia N, Zhang S, Zhu X, Liu M, Lu Y, Li N, Yang H, Tang T, Nie S, Li J, Yang F, Jiao J, Lv B, Wang W, Hu D, Hu J, Liu H, Chen C, Cheng X. Characterization of CD3+ T Lymphocytes in Human Coronary Thrombi with ST-segment Elevation Myocardial Infarction. Thromb Haemost 2024. [PMID: 39510509 DOI: 10.1055/a-2437-6111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
BACKGROUND The occurrence and development of ST-segment elevation myocardial infarction (STEMI) are accompanied by coronary atherothrombosis and occlusion, and immune responses play prominent roles in their pathogeneses. However, the causes of atherothrombosis remain elusive, and a comprehensive study of T cell-mediated immune responses in coronary thrombi from STEMI patients is lacking. OBJECTIVES The aim of this study was to determine the heterogeneity and clonality of CD3+ T lymphocytes in STEMI patients at the single-cell level. METHODS Paired single-cell RNA and T cell receptor (TCR) sequencing was performed on CD3+ T lymphocytes in the coronary thrombi and peripheral blood of STEMI patients, as well as the blood from control subjects without coronary artery disease (CAD). RESULTS Compared with those in the peripheral blood of STEMI patients, the activation, cytotoxicity, proinflammatory, and prothrombotic characteristics of CD3+ T lymphocytes in coronary thrombi were decreased, and the clonality of CD3+ T cells was increased. Compared with those from non-CAD controls, T lymphocytes from STEMI patients exhibited an upregulation of genes related to recent TCR engagement, suggesting antigen-specific stimulation in STEMI. Antigen specificity prediction using an algorithm indicated the probability of T cells from different patients binding to similar antigens for clonal expansion during STEMI. CONCLUSION This study provides a basis for exploring the cellular heterogeneity of CD3+ T lymphocytes in the coronary thrombi and peripheral blood of STEMI patients. Identifying the precise adaptive immune mechanisms driving atherothrombosis may lead to innovative therapies that selectively target the aberrant immune response, resulting in more effective treatments for STEMI.
Collapse
Affiliation(s)
- Muyang Gu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ni Xia
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Si Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinyu Zhu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Meilin Liu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuzhi Lu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Nana Li
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Haoyi Yang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tingting Tang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shaofang Nie
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jingyong Li
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fen Yang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiao Jiao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bingjie Lv
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weimin Wang
- Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Desheng Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiong Hu
- Department of Histology and Embryology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huirong Liu
- Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Chen Chen
- Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiang Cheng
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
7
|
Telemaco Contreras Colmenares M, de Oliveira Matos A, Henrique Dos Santos Dantas P, Rodrigues do Carmo Neto J, Silva-Sales M, Sales-Campos H. Unveiling the impact of TREM-2 + Macrophages in metabolic disorders. Cell Immunol 2024; 405-406:104882. [PMID: 39369473 DOI: 10.1016/j.cellimm.2024.104882] [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: 07/03/2024] [Accepted: 10/01/2024] [Indexed: 10/08/2024]
Abstract
The Triggering Receptor Expressed on Myeloid cells 2 (TREM-2) has been widely known by its anti-inflammatory activity. It can be activated in response to microbes and tissue damage, leading to phagocytosis, autophagy, cell polarization and migration, counter inflammation, and tissue repair. So far, the receptor has been largely explored in neurodegenerative disorders, however, a growing number of studies have been investigating its contribution in different pathological conditions, including metabolic diseases, in which (resident) macrophages play a crucial role. In this regard, TREM-2 + macrophages have been implicated in the onset and development of obesity, atherosclerosis, and fibrotic liver disease. These macrophages can be detected in the brain, white adipose tissue, liver, and vascular endothelium. In this review we discuss how different murine models have been demonstrating the ability of such cells to contribute to tissue and body homeostasis by phagocytosing cellular debris and lipid structures, besides contributing to lipid homeostasis in metabolic diseases. Therefore, understanding the role of TREM-2 in metabolic disorders is crucial to expand our current knowledge concerning their immunopathology as well as to foster the development of more targeted therapies to treat such conditions.
Collapse
Affiliation(s)
| | - Amanda de Oliveira Matos
- Institute of Tropical Pathology and Public Health, Universidade Federal de Goiás, Goiânia, Brazil.
| | | | | | - Marcelle Silva-Sales
- Institute of Tropical Pathology and Public Health, Universidade Federal de Goiás, Goiânia, Brazil.
| | | |
Collapse
|
|
8
|
Shah R, Murphy D, Logue M, Jerkins J, Jallouk A, Adetola K, Oluwole O, Jayani R, Biltibo E, Kim TK, Sengsayadeth S, Chinratanalab W, Kitko C, Savani B, Dholaria B. Multidisciplinary Management of Morbidities Associated with Chronic Graft-Versus-Host Disease. Clin Hematol Int 2024; 6:74-88. [PMID: 39469117 PMCID: PMC11514143 DOI: 10.46989/001c.124926] [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: 06/17/2024] [Accepted: 07/27/2024] [Indexed: 10/30/2024] Open
Abstract
Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor. While the mainstay of treatment has remained systemic immunosuppression with glucocorticoids, progress has been made within the last few years with approvals of three oral agents to treat steroid-refractory cGVHD: ibrutinib, ruxolitinib, and belumosudil. Iatrogenesis contributes a significant portion of the morbidity experienced by patients with cGVHD, primarily from glucocorticoids. This review highlights the myriad impacts of cGVHD, including and beyond the traditional organ systems captured by the National Institutes of Health Consensus Criteria, including iatrogenic complications of long-term immunosuppression. It presents the implications of cGVHD and its treatment on cardiovascular and metabolic health, bone density, endocrine function, sexual health, and ocular and pulmonary disease and outlines a framework around the comprehensive multidisciplinary approach for its evaluation and management.
Collapse
Affiliation(s)
- Rahul Shah
- Division of Cancer Medicine The University of Texas MD Anderson Cancer Center
- Department of Medicine Vanderbilt University Medical Center
| | - Danielle Murphy
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Melissa Logue
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - James Jerkins
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Andrew Jallouk
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Kassim Adetola
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Olalekan Oluwole
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Reena Jayani
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Eden Biltibo
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Tae K Kim
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Salyka Sengsayadeth
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Wichai Chinratanalab
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Carrie Kitko
- Division of Hematology/Oncology, Department of Pediatrics Vanderbilt University Medical Center
| | - Bipin Savani
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| | - Bhagirathbhai Dholaria
- Division of Hematology/Oncology, Department of Medicine Vanderbilt University Medical Center
| |
Collapse
|
|
9
|
Kerns S, Owen KA, Daamen A, Kain J, Grammer AC, Lipsky PE. Genetic association with autoimmune diseases identifies molecular mechanisms of coronary artery disease. iScience 2024; 27:110715. [PMID: 39262791 PMCID: PMC11387803 DOI: 10.1016/j.isci.2024.110715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 06/28/2024] [Accepted: 08/08/2024] [Indexed: 09/13/2024] Open
Abstract
Autoimmune patients have a significantly increased risk of developing coronary artery disease (CAD) compared to the general population. However, autoimmune patients often lack traditional risk factors for CAD and there is increasing recognition of inflammation in CAD development. In this study, we leveraged genome-wide association study (GWAS) data to understand whether there is a genetic relationship between CAD and autoimmunity. Statistical genetic comparison methods were used to identify correlated and causal SNPs between various autoimmune diseases and CAD. Pleiotropic SNPs were identified by cross-phenotype association analysis (CPASSOC) and overlap between GWAS. Causal SNPs were identified using Mendelian Randomization (MR) and Colocalization (COLOC). Using SNP-to-gene mapping, we additionally identified pleiotropic and causal genes and pathways associated between autoimmunity and CAD, which were contextualized by documentation of enrichment in individual cell types identified from coronary atherosclerotic plaques by single-cell RNA sequencing. These results provide insight into potential inflammatory therapeutic targets for CAD.
Collapse
Affiliation(s)
- Sophia Kerns
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Katherine A Owen
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Andrea Daamen
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Jessica Kain
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
- Stanford University Department of Genetics, Stanford, CA 94305, USA
| | - Amrie C Grammer
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| | - Peter E Lipsky
- AMPEL Biosolutions, LLC, Charlottesville, VA 22903, USA
- The RILITE Research Institute, Charlottesville, VA 22903, USA
| |
Collapse
|
|
10
|
Roguin A, Kobo OM. Editorial: Bridging the gap: Autoimmune diseases and cardiovascular health. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2024; 65:44-45. [PMID: 38570235 DOI: 10.1016/j.carrev.2024.03.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 03/29/2024] [Indexed: 04/05/2024]
Affiliation(s)
- Ariel Roguin
- Division of Cardiovascular Medicine, Hillel Yaffe Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
| | - Ofer M Kobo
- Division of Cardiovascular Medicine, Hillel Yaffe Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
| |
Collapse
|
|
11
|
Kumar AAW, Huangfu G, Figtree GA, Dwivedi G. Atherosclerosis as the Damocles' sword of human evolution: insights from nonhuman ape-like primates, ancient human remains, and isolated modern human populations. Am J Physiol Heart Circ Physiol 2024; 326:H821-H831. [PMID: 38305751 DOI: 10.1152/ajpheart.00744.2023] [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: 11/27/2023] [Revised: 01/25/2024] [Accepted: 01/30/2024] [Indexed: 02/03/2024]
Abstract
Atherosclerosis is the leading cause of death worldwide, and the predominant risk factors are advanced age and high-circulating low-density lipoprotein cholesterol (LDL-C). However, the findings of atherosclerosis in relatively young mummified remains and a lack of atherosclerosis in chimpanzees despite high LDL-C call into question the role of traditional cardiovascular risk factors. The inflammatory theory of atherosclerosis may explain the discrepancies between traditional risk factors and observed phenomena in current literature. Following the divergence from chimpanzees several millennia ago, loss of function mutations in immune regulatory genes and changes in gene expression have resulted in an overactive human immune system. The ubiquity of atherosclerosis in the modern era may reflect a selective pressure that enhanced the innate immune response at the cost of atherogenesis and other chronic disease states. Evidence provided from the fields of genetics, evolutionary biology, and paleoanthropology demonstrates a sort of circular dependency between inflammation, immune system functioning, and evolution at both a species and cellular level. More recently, the role of proinflammatory stimuli, somatic mutations, and the gene-environment effect appear to be underappreciated elements in the development and progression of atherosclerosis. Neurobiological stress, metabolic syndrome, and traditional cardiovascular risk factors may instead function as intermediary links between inflammation and atherosclerosis. Therefore, considering evolution as a mechanistic process and atherosclerosis as part of the inertia of evolution, greater insight into future preventative and therapeutic interventions for atherosclerosis can be gained by examining the past.
Collapse
Affiliation(s)
- Annora Ai-Wei Kumar
- Medical School, The University of Western Australia, Crawley, Western Australia, Australia
| | - Gavin Huangfu
- Medical School, The University of Western Australia, Crawley, Western Australia, Australia
- Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
- Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia
| | - Gemma A Figtree
- Cardiovascular Discovery Group, Kolling Institute of Medical Research, St. Leonards, New South Wales, Australia
- Department of Cardiology, Royal North Shore Hospital, St. Leonards, New South Wales, Australia
| | - Girish Dwivedi
- Medical School, The University of Western Australia, Crawley, Western Australia, Australia
- Department of Cardiology, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
- Harry Perkins Institute of Medical Research, Murdoch, Western Australia, Australia
| |
Collapse
|
|
12
|
Mao H, Yu Y, Wang Q, Li H. Association between pre-ICU statin use and ARDS mortality in the MIMIC-IV database: a cohort study. Front Med (Lausanne) 2023; 10:1328636. [PMID: 38188328 PMCID: PMC10768014 DOI: 10.3389/fmed.2023.1328636] [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: 10/27/2023] [Accepted: 12/06/2023] [Indexed: 01/09/2024] Open
Abstract
Background Acute respiratory distress syndrome (ARDS) is a severe condition associated with high morbidity, mortality, and healthcare costs. Despite extensive research, treatment options for ARDS are suboptimal. Methods This study encompassed patients diagnosed with ARDS from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Pre-intensive care unit (ICU) statin use was assessed as the exposure variable. Kaplan-Meier survival analysis was conducted to evaluate mortality at 30 and 90 days. Adjusted multivariable Cox models were utilized to estimate hazard ratios. Subgroup analyses and propensity score-matching (PSM) were undertaken for further validation. Results Our study comprised 10,042 participants diagnosed with ARDS, with an average age of 61.8 ± 15.3 years. Kaplan-Meier survival analysis demonstrated a significantly lower prevalence of mortality at 30 and 90 days in individuals who used statins before ICU admission. Adjusted multivariable Cox models consistently showed a significant decrease in mortality prevalence associated with pre-ICU statin use. After accounting for confounding factors, patients who used statins before ICU admission experienced a 39% reduction in 30-day mortality and 38% reduction in 90-day mortality. We found a significant decrease in ICU stay (0.84 days) for those who used statins before ICU admission. These results were supported by subgroup analyses and PSM. Conclusion This large cohort study provides evidence supporting the association between pre-ICU statin use, reduced risk of death, and shorter ICU stay in patients with ARDS, thereby suggesting the potential benefits of statin use in critically ill patients.
Collapse
Affiliation(s)
- Hui Mao
- Center for Rehabilitation Medicine, Department of Anesthesiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yi Yu
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Qianqian Wang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Pulmonary and Critical Care Medicine, Guangxi Hospital Division of The First Hospital, Sun Yat-sen University, Nanning, China
| | - Hengjie Li
- Emergency and Critical Care Center, Department of Emergency Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| |
Collapse
|
|
13
|
Mami W, Znaidi-Marzouki S, Doghri R, Ben Ahmed M, Znaidi S, Messadi E. Inflammatory Bowel Disease Increases the Severity of Myocardial Infarction after Acute Ischemia-Reperfusion Injury in Mice. Biomedicines 2023; 11:2945. [PMID: 38001946 PMCID: PMC10669621 DOI: 10.3390/biomedicines11112945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 09/26/2023] [Accepted: 09/28/2023] [Indexed: 11/26/2023] Open
Abstract
(1) Background: Increased risk of myocardial infarction (MI) has been linked to several inflammatory conditions, including inflammatory bowel disease (IBD). However, the relationship between IBD and MI remains unclear. Here, we implemented an original mouse model combining IBD and MI to determine IBD's impact on MI severity and the link between the two diseases. (2) Methods: An IBD model was established by dextran sulfate sodium (DSS) administration in drinking water, alone or with oral C. albicans (Ca) gavage. IBD severity was assessed by clinical/histological scores and intestinal/systemic inflammatory biomarker measurement. Mice were subjected to myocardial ischemia-reperfusion (IR), and MI severity was assessed by quantifying infarct size (IS) and serum cardiac troponin I (cTnI) levels. (3) Results: IBD mice exhibited elevated fecal lipocalin 2 (Lcn2) and IL-6 levels. DSS mice exhibited almost two-fold increase in IS compared to controls, with serum cTnI levels strongly correlated with IS. Ca inoculation tended to worsen DSS-induced systemic inflammation and IR injury, an observation which is not statistically significant. (4) Conclusions: This is the first proof-of-concept study demonstrating the impact of IBD on MI severity and suggesting mechanistic aspects involved in the IBD-MI connection. Our findings could pave the way for MI therapeutic approaches based on identified IBD-induced inflammatory mediators.
Collapse
Affiliation(s)
- Wael Mami
- Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
| | - Soumaya Znaidi-Marzouki
- Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LR16IPT02), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia; (S.Z.-M.); (M.B.A.)
| | - Raoudha Doghri
- Département d’Anatomie et Cytologie Pathologiques, Institut Salah-Azaeiz, Université El-Manar, Tunis 1006, Tunisia;
| | - Melika Ben Ahmed
- Laboratoire de Transmission, Contrôle et Immunobiologie des Infections (LR16IPT02), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia; (S.Z.-M.); (M.B.A.)
| | - Sadri Znaidi
- Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique (LR16IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
- Unité Biologie et Pathogénicité Fongiques, Département Mycologie, Institut Pasteur, INRA, 75015 Paris, France
| | - Erij Messadi
- Plateforme de Physiologie et Physiopathologie Cardiovasculaires (P2C), Laboratoire des Biomolécules, Venins et Applications Théranostiques (LR20IPT01), Institut Pasteur de Tunis, Université Tunis El Manar, Tunis 1068, Tunisia;
| |
Collapse
|
|
14
|
Han S, Lu H, Yu Y, Liu X, Jing F, Wang L, Zhao Y, Hou M. Hyperlipidemia in immune thrombocytopenia: a retrospective study. Thromb J 2023; 21:102. [PMID: 37784127 PMCID: PMC10544441 DOI: 10.1186/s12959-023-00545-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 09/13/2023] [Indexed: 10/04/2023] Open
Abstract
BACKGROUND Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, some patients also suffered from atherosclerosis or even infarction. Apart from activated platelets, lipid metabolism takes a large part in the formation of atherosclerosis and metabolic syndrome. The lipid metabolic state in ITP patients is still unknown. METHODS We retrospectively reviewed 302 hospitalized ITP patients in our cohort, comparing their blood lipids, bleeding symptoms, metabolic diseases and treatment responses. RESULTS We found a high proportion of ITP patients suffered from hyperlipidemia, and other metabolic diseases including cardiovascular or cerebral atherosclerosis or infarction, hypertension, and type 2 diabetes. Hyperlipidemia was associated with severe bleeding and treatment refractoriness in ITP. Statins could alleviate thrombocytopenia and bleeding severity, and facilitate ITP treatment, while improving hyperlipidemia in ITP patients. CONCLUSIONS Our present study demonstrated that lipid metabolism might play an indispensable role in ITP pathogenesis and development.
Collapse
Affiliation(s)
- Shouqing Han
- Department of Hematology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China
- Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, China
| | - Hui Lu
- Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Yafei Yu
- Department of Hematology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China
- Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, China
| | - Xinguang Liu
- Department of Hematology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China
- Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, China
| | - Fangmiao Jing
- Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China
| | - Liang Wang
- Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
- Department of Hematology, Shengli Oilfield Central Hospital, Dongying, China.
| | - Yajing Zhao
- Department of Hematology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China.
- Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan, China.
| | - Ming Hou
- Department of Hematology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, Shandong, China.
- Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Qilu Hospital of Shandong University, Jinan, China.
| |
Collapse
|
|
15
|
Zhang G, Cui X, Qin Z, Wang Z, Lu Y, Xu Y, Xu S, Tang L, Zhang L, Liu G, Wang X, Zhang J, Tang J. Atherosclerotic plaque vulnerability quantification system for clinical and biological interpretability. iScience 2023; 26:107587. [PMID: 37664595 PMCID: PMC10470306 DOI: 10.1016/j.isci.2023.107587] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 05/02/2023] [Accepted: 08/04/2023] [Indexed: 09/05/2023] Open
Abstract
Acute myocardial infarction dominates coronary artery disease mortality. Identifying bio-signatures for plaque destabilization and rupture is important for preventing the transition from coronary stability to instability and the occurrence of thrombosis events. This computational systems biology study enrolled 2,235 samples from 22 independent bulks cohorts and 14 samples from two single-cell cohorts. A machine-learning integrative program containing nine learners was developed to generate a warning classifier linked to atherosclerotic plaque vulnerability signature (APVS). The classifier displays the reliable performance and robustness for distinguishing ST-elevation myocardial infarction from chronic coronary syndrome at presentation, and revealed higher accuracy to 33 pathogenic biomarkers. We also developed an APVS-based quantification system (APVSLevel) for comprehensively quantifying atherosclerotic plaque vulnerability, empowering early-warning capabilities, and accurate assessment of atherosclerosis severity. It unraveled the multidimensional dysregulated mechanisms at high resolution. This study provides a potential tool for macro-level differential diagnosis and evaluation of subtle genetic pathological changes in atherosclerosis.
Collapse
Affiliation(s)
- Ge Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Xiaolin Cui
- School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen 518172, China
| | - Zhen Qin
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Zeyu Wang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Yongzheng Lu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Yanyan Xu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Shuai Xu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Laiyi Tang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Li Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Gangqiong Liu
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Xiaofang Wang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Jinying Zhang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| | - Junnan Tang
- Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China
- Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan 450052, China
- Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan 450052, China
| |
Collapse
|
|
16
|
Gabbiadini R, Dal Buono A, Mastrorocco E, Solitano V, Repici A, Spinelli A, Condorelli G, Armuzzi A. Atherosclerotic cardiovascular diseases in inflammatory bowel diseases: to the heart of the issue. Front Cardiovasc Med 2023; 10:1143293. [PMID: 37260950 PMCID: PMC10227624 DOI: 10.3389/fcvm.2023.1143293] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 05/04/2023] [Indexed: 06/02/2023] Open
Abstract
Atherosclerotic cardiovascular disease and stroke are the leading causes of morbidity and mortality worldwide. Along to the traditional risk factors for these diseases, chronic inflammation is known to be an important player in accelerating the process of atherosclerosis, which can result in an increased incidence of arterial thromboembolic events. As in other chronic inflammatory diseases, in the past few years, several studies suggested that subjects affected by inflammatory bowel diseases (IBD) may also be at an incremented risk of atherosclerotic disease, especially during the periods of disease's flare. Therefore, IBD treatment may assume an important role for achieving both disease remission and the control of the atherosclerotic risk. In this article we aimed to perform a comprehensive review on evidence on the increased risk of arterial thromboembolic events in patients affected by IBD and discuss the potential role of IBD therapy in reducing this risk.
Collapse
Affiliation(s)
- Roberto Gabbiadini
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Arianna Dal Buono
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Elisabetta Mastrorocco
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Virginia Solitano
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Alessandro Repici
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Gianluigi Condorelli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- Department of Cardiovascular Medicine, IRCCS Humanitas Research Hospital, Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| |
Collapse
|
|
17
|
D'Ascenzo F, Bruno F, Iannaccone M, Testa G, De Filippo O, Giannino G, Caviglia GP, Bernstein CN, De Ferrari GM, Bugianesi E, Armandi A, Ribaldone DG. Patients with inflammatory bowel disease are at increased risk of atherothrombotic disease: A systematic review with meta-analysis. Int J Cardiol 2023; 378:96-104. [PMID: 36863421 DOI: 10.1016/j.ijcard.2023.02.042] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/15/2023] [Accepted: 02/22/2023] [Indexed: 03/04/2023]
Abstract
AIMS Patients with inflammatory bowel disease (IBD) are known to be at increased risk for venous thrombosis, while their risk for arterial ischemic events is debated. The purpose of this study was to conduct a systematic review of the published literature on the risk of myocardial infarction (MI) in IBD patients and to identify any potential risk factors. METHODS The present study was performed according to PRISMA, with a systematic search on PubMed, Cochrane, and Google Scholar. Risk of MI was the primary end point, while all causes of death and stroke were secondary endpoints. Both univariate and multivariate pooled analysis were performed. RESULTS An overall population of 515,455 controls and 77,140 persons with IBD (26,852, 34.8% Crohn's disease, CD and 50,288, 65.2% ulcerative colitis, UC) was included. Mean age was similar across controls and IBD. Persons with CD and UC had lower rates of hypertension (14.5% vs. 14.6% vs. 25%), diabetes (2.9% vs. 5.2% vs. 9.2%) and dyslipidaemia (3.3% vs. 6.5% vs. 16.1%) compared to controls. Smoking did not significantly differ (17% vs. 17.5% vs. 10.6%). Pooled results of multivariate adjustment showed that, after a 5 years-follow-up, both CD and UC were at increased risk of MI (respectively HR 1.36 [1.12-1.64] and HR 1.24 [1.05-1.46]), of death (HR 1.55 [1.27-1.90] and HR 1.29 [1.01-1.64]), and of other CV disease as stroke (HR 1.22 [1.01-1.49] and HR 1.09 [1.03-1.15], all 95% CI). CONCLUSIONS Persons with IBD are at increased risk of MI, despite a lower prevalence of the classic risk factors for MI (hypertension, diabetes, dyslipidemia).
Collapse
Affiliation(s)
- Fabrizio D'Ascenzo
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital and University of Turin, Italy.
| | - Francesco Bruno
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital and University of Turin, Italy
| | - Mario Iannaccone
- Cardiology Department, San Giovanni Bosco Hospital, 10154 Turin, Italy
| | - Giulia Testa
- Department of Medical Sciences, University of Turin, Turin, Italy
| | - Ovidio De Filippo
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital and University of Turin, Italy
| | - Giuseppe Giannino
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital and University of Turin, Italy
| | | | | | - Gaetano Maria De Ferrari
- Division of Cardiology, Cardiovascular and Thoracic Department, Città della Salute e della Scienza Hospital and University of Turin, Italy
| | | | - Angelo Armandi
- Department of Medical Sciences, University of Turin, Turin, Italy
| | | |
Collapse
|
|
18
|
Duan R, Liu Y, Tang D, Lin R, Huang J, Zhao M. IgG1 Is the Optimal Subtype for Treating Atherosclerosis by Inducing M2 Macrophage Differentiation, and Is Independent of the FcγRIIA Gene Polymorphism. Int J Mol Sci 2023; 24:ijms24065932. [PMID: 36983007 PMCID: PMC10053586 DOI: 10.3390/ijms24065932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/15/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
In recent years, it has been established that atherosclerosis is an autoimmune disease. However, little is currently known about the role of FcγRIIA in atherosclerosis. Herein, we sought to investigate the relationship between FcγRIIA genotypes and the effectiveness of different IgG subclasses in treating atherosclerosis. We constructed and produced different subtypes of IgG and Fc-engineered antibodies. In vitro, we observed the effect of different subtypes of IgG and Fc-engineered antibodies on the differentiation of CD14+ monocytes from patients or healthy individuals. In vivo, Apoe-/- mice were fed a high-fat diet (HFD) for 20 weeks and administered injections of different CVI-IgG subclasses or Fc-engineered antibodies. Flow cytometry was used to assess the polarization of monocytes and macrophages. Although CVI-IgG4 reduced the release of MCP-1 compared to the other subtypes, IgG4 did not yield an anti-inflammatory effect by induction of human monocyte and macrophage differentiation in vitro. Furthermore, genetic polymorphisms of FcγRIIA were not associated with different CVI-IgG subclasses during the treatment of atherosclerosis. In vivo, CVI-IgG1 decreased Ly6Chigh monocyte differentiation and promoted M2 macrophage polarization. We also found that the secretion of IL-10 was upregulated in the CVI-IgG1-treated group, whereas V11 and GAALIE exerted no significant effect. These findings highlight that IgG1 is the optimal subtype for treating atherosclerosis, and CVI-IgG1 can induce monocyte/macrophage polarization. Overall, these results have important implications for the development of therapeutic antibodies.
Collapse
Affiliation(s)
- Rui Duan
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Yan Liu
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Dongmei Tang
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Run Lin
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Jinrong Huang
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| | - Ming Zhao
- Department of Pathophysiology, Key Lab for Shock and Microcirculation Research of Guangdong, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
| |
Collapse
|
|
19
|
Laurindo LF, de Carvalho GM, de Oliveira Zanuso B, Figueira ME, Direito R, de Alvares Goulart R, Buglio DS, Barbalho SM. Curcumin-Based Nanomedicines in the Treatment of Inflammatory and Immunomodulated Diseases: An Evidence-Based Comprehensive Review. Pharmaceutics 2023; 15:pharmaceutics15010229. [PMID: 36678859 PMCID: PMC9861982 DOI: 10.3390/pharmaceutics15010229] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/05/2023] [Accepted: 01/07/2023] [Indexed: 01/12/2023] Open
Abstract
Curcumin (CUR) is a polyphenol extracted from the rhizome of Curcuma longa that possesses potent anti-inflammatory and antioxidant potential. Despite CUR's numerous beneficial effects on human health, it has limitations, such as poor absorption. Nano-based drug delivery systems have recently been applied to improve CUR's solubility and bioavailability and potentialize its health effects. This review investigated the effects of different CUR-based nanomedicines on inflammatory and immunomodulated diseases. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR databases were searched, and the Scale for Assessment of Narrative Review Articles (SANRA) was used for quality assessment and PRISMA guidelines. Overall, 66 studies were included comprising atherosclerosis, rheumatoid arthritis (RA), Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), Huntington's disease (HD), inflammatory bowel diseases (IBD), psoriasis, liver fibrosis, epilepsy, and COVID-19. The available scientific studies show that there are many known nanoformulations with curcumin. They can be found in nanosuspensions, nanoparticles, nanoemulsions, solid lipid particles, nanocapsules, nanospheres, and liposomes. These formulations can improve CUR bioavailability and can effectively be used as adjuvants in several inflammatory and immune-mediated diseases such as atheroma plaque formation, RA, dementia, AD, PD, MS, IBD, psoriasis, epilepsy, COVID-19, and can be used as potent anti-fibrotic adjuvants in fibrotic liver disease.
Collapse
Affiliation(s)
- Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
| | - Gabriel Magno de Carvalho
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
| | - Bárbara de Oliveira Zanuso
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
| | - Maria Eduardo Figueira
- Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Rosa Direito
- Laboratory of Systems Integration Pharmacology, Clinical & Regulatory Science, Research Institute for Medicines (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
- Faculty of Pharmacy, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal
| | - Ricardo de Alvares Goulart
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
| | - Daiene Santos Buglio
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marília (UNIMAR), Avenida Hygino Muzzy Filho, 1001, Marília, São Paulo 17525-902, Brazil
- Department of Biochemistry and Nutrition, School of Food and Technology of Marília (FATEC), Avenida Castro Alves, 62, Marília, São Paulo 17500-000, Brazil
- Correspondence: ; Tel.: +55-14-99655-3190
| |
Collapse
|
|
20
|
RELATIONSHIPS BETWEEN LIPID PROFILE AND COMPLETE BLOOD CELL COUNT PARAMETERS. ACTA MEDICA LEOPOLIENSIA 2022. [DOI: 10.25040/aml2022.3-4.97] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2023]
Abstract
Aim. Given that blood cells play an important role in both atherogenesis and lipid metabolism, the research aimed to assess the specifics of the relationship between the parameters of the blood lipid spectrum and the complete blood count (CBC).
Materials and Methods. A total of 475 individuals (245 female and 230 male) were included in the study, who simultaneously underwent CBC and determination of lipid profile, namely: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Statistical processing of the obtained data was carried out using the "Statistica for Windows 6.0" software package (Statsoft, USA).
Results. An increase in levels of TC and LDL-C was associated with an increase in the count of lymphocytes and erythrocytes. A rise in VLDL-C and, accordingly, TG levels, as well as a decrease in the level of HDL-C, were associated with an increase in the total leukocyte count in the blood without a significant change in the ratio of their different types, and an increase in erythrocyte sedimentation rate. The count of platelets was directly related to the level of LDL-C and increased in the case of a combination of elevated levels of LDL-C and TG.
Discussion. The obtained results indicate that the disposal of excess lipoproteins is based on various types of immune reactions. An increase in the levels of VLDL-C and TG is associated with the development of a nonspecific leukocyte reaction, and an increase in LDL-C levels is associated with a more specific platelet-lymphocytic response. A simultaneous increase in LDL-C and TG levels can be associated with the development of both specific and non-specific immune reactions. An increase in the level of HDL-C leads to a decrease in the intensity of innate and adaptive immune responses. Therefore, the lipid profile of patients should be evaluated by taking into account the blood cell counts, especially in the process of hypolipidemic treatment.
Conclusions. An atherogenic lipid profile is associated with increased counts of all blood cells, reflecting specific and nonspecific immune reactions in response to elevated levels of various lipid groups. Platelets play an important role in lipid metabolism.
Connection of the research with scientific programs, plans, and topics. The study is a fragment of the planned scientific research of the Department of Internal Medicine No. 2 of the Danylo Halytsky Lviv National Medical University: "Peculiarities and markers of the course of internal diseases under conditions of combination with metabolic syndrome and metabolically associated fatty liver disease", state registration number: 0122U000165.
Collapse
|
|
21
|
There is urgent need to treat atherosclerotic cardiovascular disease risk earlier, more intensively, and with greater precision: A review of current practice and recommendations for improved effectiveness. Am J Prev Cardiol 2022; 12:100371. [PMID: 36124049 PMCID: PMC9482082 DOI: 10.1016/j.ajpc.2022.100371] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 07/10/2022] [Accepted: 08/05/2022] [Indexed: 12/12/2022] Open
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is epidemic throughout the world and is etiologic for such acute cardiovascular events as myocardial infarction, ischemic stroke, unstable angina, and death. ASCVD also impacts risk for dementia, chronic kidney disease peripheral arterial disease and mobility, impaired sexual response, and a host of other visceral impairments that adversely impact the quality and rate of progression of aging. The relationship between low-density lipoprotein cholesterol (LDL-C) and risk for ASCVD is one of the most highly established and investigated issues in the entirety of modern medicine. Elevated LDL-C is a necessary condition for atherogenesis induction. Basic scientific investigation, prospective longitudinal cohorts, and randomized clinical trials have all validated this association. Yet despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs. Herein we discuss the need to greatly intensify efforts to reduce risk, decrease disease burden, and provide more comprehensive and earlier risk assessment to optimally prevent ASCVD and its complications. Evidence is presented to support that treatment should aim for far lower goals in cholesterol management, should take into account many more factors than commonly employed today and should begin significantly earlier in life.
Collapse
|
|
22
|
Liu TY, Liao WL, Wang TY, Chan CJ, Chang JG, Chen YC, Lu HF, Yang HH, Chen SY, Tsai FJ. Genome-wide association study of hyperthyroidism based on electronic medical record from Taiwan. Front Med (Lausanne) 2022; 9:830621. [PMID: 35991636 PMCID: PMC9390483 DOI: 10.3389/fmed.2022.830621] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 06/27/2022] [Indexed: 11/13/2022] Open
Abstract
Excess thyroid hormones have complex metabolic effects, particularly hyperthyroidism, and are associated with various cardiovascular risk factors. Previous candidate gene studies have indicated that genetic variants may contribute to this variable response. Electronic medical record (EMR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform the disease comorbidity development. In this study, we combined electronic medical record (EMR) -derived phenotypes and genotype information to conduct a genome-wide analysis of hyperthyroidism in a 35,009-patient cohort in Taiwan. Diagnostic codes were used to identify 2,767 patients with hyperthyroidism. Our genome-wide association study (GWAS) identified 44 novel genomic risk markers in 10 loci on chromosomes 2, 6, and 14 (P < 5 × 10–14), including CTLA4, HCP5, HLA-B, POU5F1, CCHCR1, HLA-DRA, HLA-DRB9, TSHR, RPL17P3, and CEP128. We further conducted a comorbidity analysis of our results, and the data revealed a strong correlation between hyperthyroidism patients with thyroid storm and stroke. In this study, we demonstrated application of the PheWAS using large EMR biobanks to inform the comorbidity development in hyperthyroidism patients. Our data suggest significant common genetic risk factors in patients with hyperthyroidism. Additionally, our results show that sex, body mass index (BMI), and thyroid storm are associated with an increased risk of stroke in subjects with hyperthyroidism.
Collapse
Affiliation(s)
- Ting-Yuan Liu
- Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan
- Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Ling Liao
- College of Chinese Medicine, Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
- Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan
- Genetics Center, Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Tzu-Yuan Wang
- Department of Internal Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Division of Endocrinology, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Jung Chan
- Genetics Center, Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Jan-Gowth Chang
- Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Chia Chen
- Center for Precision Medicine, China Medical University Hospital, Taichung, Taiwan
- Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | - Hsing-Fang Lu
- Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
| | | | - Shih-Yin Chen
- Genetics Center, Medical Research, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
- *Correspondence: Shih-Yin Chen
| | - Fuu-Jen Tsai
- Genetics Center, Medical Research, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan
- Fuu-Jen Tsai
| |
Collapse
|
|
23
|
Xu J, Chen C, Yang Y. Identification and Validation of Candidate Gene Module Along With Immune Cells Infiltration Patterns in Atherosclerosis Progression to Plaque Rupture via Transcriptome Analysis. Front Cardiovasc Med 2022; 9:894879. [PMID: 35811739 PMCID: PMC9257180 DOI: 10.3389/fcvm.2022.894879] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 05/19/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To explore the differentially expressed genes (DEGs) along with infiltrating immune cells landscape and their potential mechanisms in the progression of atherosclerosis from onset to plaque rupture. Methods In this study, three atherosclerosis-related microarray datasets were downloaded from the NCBI-GEO database. The gene set enrichment analysis (GSEA) was performed for interpreting the biological insights of gene expression data. The CIBERSORTx algorithm was applied to infer the relative proportions of infiltrating immune cells of the atherosclerotic samples. DEGs of the datasets were screened using R. The protein interaction network was constructed via STRING. The cluster genes were analyzed by the Cytoscape software. Gene ontology (GO) enrichment was performed via geneontology.org. The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm and receiver operating characteristics (ROC) analyses were performed to build machine learning models for differentiating atherosclerosis status. The Pearson correlation analysis was carried out to illustrate the relationship between cluster genes and immune cells. The expression levels of the cluster genes were validated in two external cohorts. Transcriptional factors and drug-gene interaction analysis were performed to investigate the promising targets for atherosclerosis intervention. Results Pathways related to immunoinflammatory responses were identified according to GSEA analysis, and the detailed fractions infiltrating immune cells were compared between the early and advanced atherosclerosis. Additionally, we identified 170 DEGs in atherosclerosis progression (|log2FC|≥1 and adjusted p < 0.05). They were mainly enriched in GO terms relating to inflammatory response and innate immune response. A cluster of nine genes, such as ITGB2, C1QC, LY86, CTSS, C1QA, CSF1R, LAPTM5, VSIG4, and CD163, were found to be significant, and their correlations with infiltrating immune cells were calculated. The cluster genes were also validated to be upregulated in two external cohorts. Moreover, C1QA and ITGB2 may exert pathogenic functions in the entire process of atherogenesis. Conclusions We reanalyzed the transcriptomic signature of atherosclerosis development from onset to plaque rupture along with the landscape of the immune cell, as well as revealed new insights and specific prospective DEGs for the investigation of disease-associated dynamic molecular processes and their regulations with immune cells.
Collapse
Affiliation(s)
- Jing Xu
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital and National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Cheng Chen
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital and National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuejin Yang
- State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital and National Center for Cardiovascular Diseases, Beijing, China
- Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- *Correspondence: Yuejin Yang
| |
Collapse
|
|
24
|
LINC00460 Stimulates the Proliferation of Vascular Endothelial Cells by Downregulating miRNA-24-3p. DISEASE MARKERS 2022; 2022:2524156. [PMID: 35222741 PMCID: PMC8881155 DOI: 10.1155/2022/2524156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/23/2021] [Indexed: 11/18/2022]
Abstract
Objective To clarify the effect of LINC00460 on mediating the proliferative ability of vascular endothelial cells (ECs) by targeting microRNA-24-3p (miRNA-24-3p), thus influencing the progression of atherosclerotic diseases. Methods Relative levels of LINC00460 and miRNA-24-3p in ECs induced with different doses of ox-LDL (oxidized low density lipoprotein) for different time points were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Influences of LINC00460 and miRNA-24-3p on the viability of ECs were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assay. Through dual-luciferase reporter gene assay, the binding between LINC00460 and miRNA-24-3p was evaluated. At last, rescue experiments were performed to identify the function of the LINC00460/miRNA-24-3p axis in regulating the proliferative ability of ECs. Results LINC00460 was upregulated after ox-LDL treatment in a dose- and time-dependent manner. Viability of ECs gradually increased with the prolongation of ox-LDL treatment and the treatment of increased dose. The overexpression of LINC00460 enhanced the viability and EdU-positive rate in ECs treated with ox-LDL. miRNA-24-3p was the direct target of LINC00460, which was negatively regulated by LINC00460. miRNA-24-3p was downregulated with the prolongation of ox-LDL treatment. The overexpression of miRNA-24-3p could reverse the effect of LINC00460 on regulating the proliferative ability of ECs. Conclusions LINC00460 regulates the proliferative ability of ECs and thus the occurrence and development of coronary atherosclerotic diseases by targeting miRNA-24-3p.
Collapse
|
|
25
|
Serum anti-SERPINE1 antibody as a potential biomarker of acute cerebral infarction. Sci Rep 2021; 11:21772. [PMID: 34741085 PMCID: PMC8571331 DOI: 10.1038/s41598-021-01176-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 10/19/2021] [Indexed: 11/11/2022] Open
Abstract
The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.
Collapse
|
|
26
|
Ahmadi A, Panahi Y, Johnston TP, Sahebkar A. Antidiabetic drugs and oxidized low-density lipoprotein: A review of anti-atherosclerotic mechanisms. Pharmacol Res 2021; 172:105819. [PMID: 34400317 DOI: 10.1016/j.phrs.2021.105819] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/12/2021] [Accepted: 08/12/2021] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease is one of the leading causes of mortality globally. Atherosclerosis is an important step towards different types of cardiovascular disease. The role of oxidized low-density lipoprotein (oxLDL) in the initiation and progression of atherosclerosis has been thoroughly investigated in recent years. Moreover, clinical trials have established that diabetic patients are at a greater risk of developing atherosclerotic plaques. Hence, we aimed to review the clinical and experimental impacts of various classes of antidiabetic drugs on the circulating levels of oxLDL. Metformin, pioglitazone, and dipeptidyl peptidase-4 inhibitors were clinically associated with a suppressive effect on oxLDL in patients with impaired glucose tolerance. However, there is an insufficient number of studies that have clinically evaluated the relationship between oxLDL and newer agents such as agonists of glucagon-like peptide 1 receptor or inhibitors of sodium-glucose transport protein 2. Next, we attempted to explore the multitude of mechanisms that antidiabetic agents exert to counter the undesirable effects of oxLDL in macrophages, endothelial cells, and vascular smooth muscle cells. In general, antidiabetic drugs decrease the uptake of oxLDL by vascular cells and reduce subsequent inflammatory signaling, which prevents macrophage adhesion and infiltration. Moreover, these agents suppress the oxLDL-induced transformation of macrophages into foam cells by either inhibiting oxLDL entrance, or by facilitating its efflux. Thus, the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of antidiabetic agents abrogate changes induced by oxLDL, which can be extremely beneficial in controlling atherosclerosis in diabetic patients.
Collapse
Affiliation(s)
- Ali Ahmadi
- Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Yunes Panahi
- Pharmacotherapy Department, Faculty of Pharmacy, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - 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; School of Medicine, The University of Western Asutralia, Perth, Australia; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 9177948567, Iran.
| |
Collapse
|
|
27
|
Autoimmune Rheumatic Diseases and Vascular Function: The Concept of Autoimmune Atherosclerosis. J Clin Med 2021; 10:jcm10194427. [PMID: 34640445 PMCID: PMC8509415 DOI: 10.3390/jcm10194427] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/18/2022] Open
Abstract
Autoimmune rheumatic diseases (AIRDs) with unknown etiology are increasing in incidence and prevalence. Up to 5% of the population is affected. AIRDs include rheumatoid arthritis, system lupus erythematosus, systemic sclerosis, and Sjögren's syndrome. In patients with autoimmune diseases, the immune system attacks structures of its own body, leading to widespread tissue and organ damage, which, in turn, is associated with increased morbidity and mortality. One third of the mortality associated with autoimmune diseases is due to cardiovascular diseases. Atherosclerosis is considered the main underlying cause of cardiovascular diseases. Currently, because of finding macrophages and lymphocytes at the atheroma, atherosclerosis is considered a chronic immune-inflammatory disease. In active inflammation, the liberation of inflammatory mediators such as tumor necrotic factor alpha (TNFa), interleukine-6 (IL-6), IL-1 and other factors like T and B cells, play a major role in the atheroma formation. In addition, antioxidized, low-density lipoprotein (LDL) antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF) are higher in the atherosclerotic patients. Traditional risk factors like gender, age, hypercholesterolemia, smoking, diabetes mellitus, and hypertension, however, do not alone explain the risk of atherosclerosis present in autoimmune diseases. This review examines the role of chronic inflammation in the etiology-and progression-of atherosclerosis in autoimmune rheumatic diseases. In addition, discussed here in detail are the possible effects of autoimmune rheumatic diseases that can affect vascular function. We present here the current findings from studies that assessed vascular function changes using state-of-the-art techniques and innovative endothelial function biomarkers.
Collapse
|
|
28
|
A Pilot Study: Hypertension, Endothelial Dysfunction and Retinal Microvasculature in Rheumatic Autoimmune Diseases. J Clin Med 2021; 10:jcm10184067. [PMID: 34575178 PMCID: PMC8467719 DOI: 10.3390/jcm10184067] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/26/2021] [Accepted: 09/07/2021] [Indexed: 12/14/2022] Open
Abstract
Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
Collapse
|
|
29
|
Ekmen N, Can G, Yozgat A, Can H, Bayraktar MF, Demirkol ME, Akdoğan Kayhan M, Sasani H. Evaluation of epicardial adipose tissue and carotid intima-media thickness as a marker of atherosclerosis in patients with inflammatory bowel disease. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 113:643-648. [PMID: 33393342 DOI: 10.17235/reed.2020.7394/2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIM this study aimed to compare carotid intima media (CIMT) and epicardial adipose tissue (EAT) measurements, which are considered as markers for the detection of early atherosclerosis in healthy controls and inflammatory bowel disease (IBD) cases. METHODS a total of 60 IBD patients (25 Crohn's disease and 35 ulcerative colitis) and 60 healthy patients (as a control group) were included in the study. The measurements of CIMT and EAT were performed using echocardiography and ultrasonography, respectively. Statistical analysis was used to determine the relationship between the parameters. RESULTS the thickness of bilateral (right and left) CIMT and EAT were significantly higher in IBD than in the control group (p < 0.05). There was a positive correlation between EAT and bilateral (right and left) CIMT in IBD patients (p < 0.05). CONCLUSION IBD is associated with an increased thickness of EAT and CIMT. Chronic inflammation in IBD may increase the risk of atherosclerotic heart disease. Thus, only measuring the thickness of EAT and CIMT can be used as an objective, easy, simple, affordable, non-invasive and accessible assessment method in order to screen for this risk.
Collapse
Affiliation(s)
- Nergiz Ekmen
- Gastroenterogy, Faculty of Medicine. Gazi University, Turkey
| | - Güray Can
- Gastroenterology, Faculty of Medicine. Abant Izzet Baysal University, Turkey
| | - Ahmet Yozgat
- Gastroenterology, Faculty of Medicine. Ufuk University, Türkiye
| | - Hatice Can
- Nephrology, Faculty of Medicine. Inönü University, Turkey
| | | | | | - Meral Akdoğan Kayhan
- Gastroenterology, Ankara Bilkent City Hospital. University of Health Sciences, Turkey
| | - Hadi Sasani
- Radiology, Faculty of Medicine. Tekirdağ Namik Kemal University, Turkey
| |
Collapse
|
|
30
|
Tabares-Guevara JH, Villa-Pulgarin JA, Hernandez JC. Atherosclerosis: immunopathogenesis and strategies for immunotherapy. Immunotherapy 2021; 13:1231-1244. [PMID: 34382409 DOI: 10.2217/imt-2021-0009] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Atherosclerosis, a chronic inflammatory condition in which atheroma accumulates within the intima of the arterial wall, is a life-threatening manifestation of cardiovascular disease, due to atheroma rupture, chronic luminal narrowing and thrombosis. Current knowledge of the role of a protective immune response in atherosclerotic lesions has provided promising opportunities to develop new immunotherapeutic strategies. In particular, Tregs exert an atheroprotective role by releasing anti-inflammatory cytokines (IL-10/TGF-β) and suppressing autoreactive T lymphocytes. In vivo animal experiments have shown that this can be achieved by developing vaccines that stimulate immunological tolerance to atheroma antigens. Here, we present an overview of the current knowledge of the proatherogenic immune response, and we discuss the strategies currently used as immunoregulatory therapy.
Collapse
Affiliation(s)
| | - Janny A Villa-Pulgarin
- Facultad de Ciencias de la Salud, Corporación Universitaria Remington, Medellín, Colombia
| | - Juan C Hernandez
- Infettare, Facultad de Medicina, Universidad Cooperativa de Colombia, Medellín, Colombia
| |
Collapse
|
|
31
|
Wang H, Lu H, Zhang XM, Goto KI, Kobayashi E, Yoshida Y, Adachi A, Matsutani T, Iwadate Y, Mine S, Machida T, Sata M, Yamagishi K, Iso H, Sawada N, Tsugane S, Kamitsukasa I, Wada T, Aotsuka A, Sugimoto K, Takizawa H, Kashiwado K, Shin H, Tomiyoshi G, Nakamura R, Shinmen N, Kuroda H, Xu A, Hiwasa T. Association of serum levels of antibodies against ALDOA and FH4 with transient ischemic attack and cerebral infarction. BMC Neurol 2021; 21:274. [PMID: 34243715 PMCID: PMC8268454 DOI: 10.1186/s12883-021-02301-w] [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: 03/18/2020] [Accepted: 06/28/2021] [Indexed: 12/12/2022] Open
Abstract
Background Ischemic stroke, including transient ischemic attack (TIA) and acute-phase cerebral infarction (aCI), is a serious health problem in the aging society. Thus, this study aimed to identify TIA and aCI biomarkers. Methods In 19 patients with TIA, candidate antigens recognized by serum IgG autoantibodies were screened using a human aortic endothelial cell cDNA library. Through amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA), serum antibody levels against the candidate antigens were examined in healthy donor (HD), TIA, and aCI cohorts (n = 285, 92, and 529). The plasma antibody levels in the Japan Public Health Center-based Prospective Cohort Study (1991–1993) were also examined. Results The candidate antigens were aldolase A (ALDOA) and fumarate hydratase (FH). In AlphaLISA, patients with TIA or aCI had higher anti-ALDOA antibody (ALDOA-Ab) and anti-FH antibody (FH-Ab) levels than the HDs (P < 0.05). In a multivariate logistic regression analysis, the ALDOA-Ab (odds ratio [OR]: 2.46, P = 0.0050) and FH-Ab (OR: 2.49, P = 0.0037) levels were independent predictors of TIA. According to the case–control study, the ALDOA-Ab (OR: 2.50, P < 0.01) and FH-Ab (OR: 2.60, P < 0.01) levels were associated with aCI risk. In a correlation analysis, both ALDOA-Abs and FH-Abs were well associated with hypertension, coronary heart disease, and habitual smoking. These antibody levels also correlated well with maximum intima–media thickness, which reflects atherosclerotic stenosis. Conclusions ALDOA-Abs and FH-Abs can be novel potential biomarkers for predicting atherosclerotic TIA and aCI.
Collapse
Affiliation(s)
- Hao Wang
- Stroke Center, the First Affiliated Hospital, Jinan University, NO. 613, West Huangpu Ave., Tianhe Dist., Guangzhou, 510630, China.,Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Hao Lu
- Stroke Center, the First Affiliated Hospital, Jinan University, NO. 613, West Huangpu Ave., Tianhe Dist., Guangzhou, 510630, China
| | - Xiao-Meng Zhang
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Ken-Ichiro Goto
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan
| | - Eiichi Kobayashi
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.,Comprehensive Stroke Center, Chiba University Hospital, Chiba, 260-8677, Japan
| | - Yoichi Yoshida
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.,Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.,Comprehensive Stroke Center, Chiba University Hospital, Chiba, 260-8677, Japan
| | - Akihiko Adachi
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan
| | - Tomoo Matsutani
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan
| | - Yasuo Iwadate
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.,Comprehensive Stroke Center, Chiba University Hospital, Chiba, 260-8677, Japan
| | - Seiichiro Mine
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.,Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba, 287-0003, Japan.,Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba, 290-0512, Japan
| | - Toshio Machida
- Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba, 290-0512, Japan.,Department of Neurosurgery, Eastern Chiba Medical Center, Chiba, 283-8686, Japan
| | - Mizuki Sata
- Department of Public Health, Social Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Kazumasa Yamagishi
- Department of Public Health Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Hiroyasu Iso
- Department of Public Health, Social Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Norie Sawada
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
| | - Ikuo Kamitsukasa
- Department of Neurology, Chiba Rosai Hospital, Chiba, 290-0003, Japan.,Department of Neurology, Chibaken Saiseikai Narashino Hospital, Chiba, 275-8580, Japan
| | - Takeshi Wada
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, 260-0852, Japan
| | - Akiyo Aotsuka
- Department of Internal Medicine, Chiba Aoba Municipal Hospital, Chiba, 260-0852, Japan
| | - Kazuo Sugimoto
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.,Department of Neurology, Dongzhimen Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Hirotaka Takizawa
- Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba, 260-0025, Japan
| | - Koichi Kashiwado
- Department of Neurology, Kashiwado Hospital, Chiba, 260-0854, Japan
| | - Hideo Shin
- Department of Neurosurgery, Higashi Funabashi Hospital, Chiba, 274-0065, Japan
| | - Go Tomiyoshi
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.,Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, 340-0203, Japan
| | - Rika Nakamura
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.,Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, 340-0203, Japan
| | - Natsuko Shinmen
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.,Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, 340-0203, Japan
| | - Hideyuki Kuroda
- Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama, 340-0203, Japan
| | - Anding Xu
- Stroke Center, the First Affiliated Hospital, Jinan University, NO. 613, West Huangpu Ave., Tianhe Dist., Guangzhou, 510630, China.
| | - Takaki Hiwasa
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan. .,Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan. .,Comprehensive Stroke Center, Chiba University Hospital, Chiba, 260-8677, Japan.
| |
Collapse
|
|
32
|
Lin CY, Chen HA, Wu CH, Su YJ, Hsu TC, Hsu CY. Is Behçet's syndrome associated with an increased risk of ischemic heart disease? A real-world evidence in Taiwan. Arthritis Res Ther 2021; 23:161. [PMID: 34088352 PMCID: PMC8176589 DOI: 10.1186/s13075-021-02543-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 05/21/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND A variety of chronic inflammatory diseases are linked to ischemic heart disease (IHD); however, this association is less well studied in patients with Behçet's syndrome (BS). The primary objective of this study was to examine the impact of BS on the risk of IHD. The secondary objective was to estimate the long-term mortality risk in patients with BS. METHODS Using a retrospective cohort design based on the Taiwan National Health Insurance Database, patients diagnosed with BS between 2000 and 2013, without prior history of IHD, were compared to non-BS individuals. The BS and non-BS cohorts were matched with a 1:2 ratio by propensity score, accounting for the following confounders: age, sex, year of index date, comorbidities, and drug exposure. Cox proportional hazard regression was used to derive the hazard ratio (HR) for IHD and mortality. The long-term survival rate was estimated using the Kaplan-Meier method. RESULTS After propensity score matching, a total of 1554 patients newly diagnosed with BS and 3108 control subjects were identified. The incidence rate of IHD in the BS and control groups was 2.7 and 2.9 per 1000 person-years, respectively. The risk of IHD was comparable between BS and control cohorts [adjusted HR, 1.03; 95% confidence interval (CI), 0.66 to 1.62]. The 5- and 10-year survival rate of BS patients was 96.8% and 95.0%, respectively. Patients with BS exhibited a significantly higher risk of mortality than the sex- and age-matched general population (adjusted HR, 1.73; 95% CI, 1.30 to 2.32). CONCLUSION Unlike other chronic systemic autoimmune disorders, BS does not appear to be associated with an excess risk of IHD.
Collapse
Affiliation(s)
- Chun-Yu Lin
- Division of Rheumatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No.138, Sheng Li Road, Tainan, 704 Taiwan
| | - Hung-An Chen
- Division of Allergy-Immunology-Rheumatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
- Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Chun-Hsin Wu
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yu-Jih Su
- Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tsai-Ching Hsu
- Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan
| | - Chung-Yuan Hsu
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, No. 123, Ta Pei Road, Niao Sung District, Kaohsiung, 83301 Taiwan
| |
Collapse
|
|
33
|
Chung JH. Antithyroid Drug Treatment in Graves' Disease. Endocrinol Metab (Seoul) 2021; 36:491-499. [PMID: 34130446 PMCID: PMC8258321 DOI: 10.3803/enm.2021.1070] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 12/21/2022] Open
Abstract
Graves' disease is associated with thyrotropin (TSH) receptor stimulating antibody, for which there is no therapeutic agent. This disease is currently treated through inhibition of thyroid hormone synthesis or destruction of the thyroid gland. Recurrence after antithyroid drug (ATD) treatment is common. Recent studies have shown that the longer is the duration of use of ATD, the higher is the remission rate. Considering the relationship between clinical outcomes and iodine intake, recurrence of Graves' disease is more common in iodine-deficient areas than in iodine-sufficient areas. Iodine restriction in an iodine-excessive area does not improve the effectiveness of ATD or increase remission rates. Recently, Danish and Korean nationwide studies noted significantly higher prevalence of birth defects in newborns exposed to ATD during the first trimester compared to that of those who did not have such exposure. The prevalence of birth defects was lowest when propylthiouracil (PTU) was used and decreased by only 0.15% when methimazole was changed to PTU in the first trimester. Therefore, it is best not to use ATD in the first trimester or to change to PTU before pregnancy.
Collapse
Affiliation(s)
- Jae Hoon Chung
- Division of Endocrinology & Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
34
|
Tarantino G, Citro V, Balsano C, Capone D. Age and Interleukin-15 Levels Are Independently Associated With Intima-Media Thickness in Obesity-Related NAFLD Patients. Front Med (Lausanne) 2021; 8:634962. [PMID: 34095164 PMCID: PMC8175965 DOI: 10.3389/fmed.2021.634962] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/06/2021] [Indexed: 01/06/2023] Open
Abstract
Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34-53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15. Anthropometric measures, metabolic profile, and serum inflammatory markers, as well as the levels of IL-15, MCP-1, b FGF, and GM-CSF, were analyzed by a bead-based assay. IMT, HS, subcutaneous, and visceral adipose tissues were detected by ultrasonography. The IL-15 levels of the obese patients were increased with respect to those of 44 young healthy subjects, i.e., 2.77 (1.21-4.8) vs. 1.55 (1-2.4) pg/mL (P = 0.002). In the univariate analysis, IL-15 levels were associated to IMT and to those of MCP-1, b FGF, and GM-CSF, without any relation to other inflammatory markers such as CRP and ferritin, except fibrinogen. In the multivariate analysis, after adjusting the HS severity for the extent of visceral adiposity, a dramatic change in prediction of IMT by HS was shown (β from 0.29 to 0.10, P from 0.008 to 0.37). When the visceral adipose tissue was combined with IL-15, on the one hand, and the well-known coronary artery disease (CAD) risk factors-i.e., age, gender, smoking status, HDL-cholesterol concentrations, triglycerides levels, and HOMA-on the other, only age and IL-15 remained the predictors of IMT (β = 0.60, P = 0.0001 and β = 0.25, P = 0.024, respectively). There was no association of IL-15 with various anthropometric parameters nor with body fat distribution and severity of HS, also after adjusting for age. Age is resulted to be the main factor in the prediction of IMT and thus of early atherosclerosis. The prediction of IMT by IL-15 coupled with the lack of prediction by the well-known CAD risks is in agreement with recent data, which emphasizes the main role of the immune system in the onset/worsening of atherosclerosis, even though the role of visceral adiposity should be further deepened. Age and IL-15 levels were both predictors of early atherosclerosis in this population of obese patients with NAFLD, suggesting a possible role of this cytokine in the atherosclerosis process.
Collapse
Affiliation(s)
- Giovanni Tarantino
- Department of Clinical Medicine and Surgery, Federico II University Medical School of Naples, Naples, Italy
| | - Vincenzo Citro
- Department of General Medicine, “Umberto I” Hospital, Nocera Inferiore, Italy
| | - Clara Balsano
- Department of Clinical Medicine, Life, Health and Environmental Sciences-MESVA, University of L'Aquila, L'Aquila, Italy
| | | |
Collapse
|
|
35
|
Assessment of medullary and extramedullary myelopoiesis in cardiovascular diseases. Pharmacol Res 2021; 169:105663. [PMID: 33979688 DOI: 10.1016/j.phrs.2021.105663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 04/15/2021] [Accepted: 05/04/2021] [Indexed: 11/23/2022]
Abstract
Recruitment of innate immune cells and their accumulation in the arterial wall and infarcted myocardium has been recognized as a central feature of atherosclerosis and cardiac ischemic injury, respectively. In both, steady state and under pathological conditions, majority of these cells have a finite life span and are continuously replenished from haematopoietic stem/progenitor cell pool residing in the bone marrow and extramedullary sites. While having a crucial role in the cardiovascular disease development, proliferation and differentiation of innate immune cells within haematopoietic compartments is greatly affected by the ongoing cardiovascular pathology. In the current review, we summarize key cells, processes and tissue compartments that are involved in myelopoiesis under the steady state, during atherosclerosis development and in myocardial infarction.
Collapse
|
|
36
|
Heslinga M, Nielen MMJ, Smulders Y, Simsek S, Nurmohamed MT. Amplified prevalence and incidence of cardiovascular disease in patients with inflammatory arthritis and coexistent autoimmune disorders. Rheumatology (Oxford) 2021; 59:2448-2454. [PMID: 31953945 DOI: 10.1093/rheumatology/kez650] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 11/29/2019] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE This study aims to assess the prevalence proportion and incidence rate of cardiovascular morbidity in patients with inflammatory arthritis compared with that in controls, and to determine whether the co-existence of multiple autoimmune disorders is associated with an amplified risk of cardiovascular disease. METHODS Data from the Nivel Primary Care Database were used to assess prevalence proportion and incidence rate of cardiovascular disease in patients with inflammatory arthritis only, patients with inflammatory arthritis coexistent with another autoimmune disorder, and controls. Hazard ratios were calculated using Cox regression models. RESULTS The prevalence proportions in inflammatory arthritis patients were increased for type 1 diabetes [odds ratio (OR) 1.80, 95% CI: 1.27, 2.55], hypothyroidism (OR 1.49, 95% CI: 1.37, 1.61), psoriasis (OR 2.72, 95% CI: 2.49, 2.97) and IBD (OR 2.64, 95% CI: 2.28, 3.07) compared with that in controls. Cardiovascular disease prevalence (OR 1.34, 95% CI: 1.28, 1.41) and incidence rates (incidence rate ratio 1.3, 95% CI: 1.23, 1.41) were higher in inflammatory arthritis patients compared with that in controls, and were further increased in the presence of a second autoimmune disorder. The hazard ratio for cardiovascular disease was 1.32 (95% CI: 1.23, 1.41) for patients with inflammatory arthritis only, and 1.49 (95% CI: 1.31, 1.68) for patients with inflammatory arthritis co-existent with another autoimmune disorder. CONCLUSION The amplification of cardiovascular disease risk in inflammatory arthritis patients with multiple autoimmune disorders warrants greater awareness, and since autoimmune disorders often co-exist, the need for cardiovascular risk management in these patients is once again emphasized.
Collapse
Affiliation(s)
- Maaike Heslinga
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center
- Reade, Amsterdamthe Netherlands
| | - Mark M J Nielen
- NIVEL (Netherlands Institute for Health Services Research), Utrechtthe Netherlands
| | - Yvo Smulders
- Department of Internal Medicine, VU University Medical Center, Amsterdamthe Netherlands
| | - Suat Simsek
- Department of Internal Medicine, VU University Medical Center, Amsterdamthe Netherlands.,Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands
| | - Mike T Nurmohamed
- Department of Rheumatology, Amsterdam Rheumatology and Immunology Center
- Reade, Amsterdamthe Netherlands.,Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, the Netherlands
| |
Collapse
|
|
37
|
Zhang G, Cai Q, Zhou H, He C, Chen Y, Zhang P, Wang T, Xu L, Yan J. OxLDL/β2GPI/anti‑β2GPI Ab complex induces inflammatory activation via the TLR4/NF‑κB pathway in HUVECs. Mol Med Rep 2020; 23:148. [PMID: 33355374 PMCID: PMC7789093 DOI: 10.3892/mmr.2020.11787] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 10/22/2020] [Indexed: 02/07/2023] Open
Abstract
Patients with antiphospholipid syndrome have been identified to have higher incidence rates of atherosclerosis (AS) due to the elevated levels of anti-β2-glycoprotein I (β2GPI) antibody (Ab). Our previous studies revealed that the anti-β2GPI Ab formed a stable oxidized low-density lipoprotein (oxLDL)/β2GPI/anti-β2GPI Ab complex, which accelerated AS development by promoting the accumulation of lipids in macrophages and vascular smooth muscle cell. However, the effects of the complex on endothelial cells, which drive the initiation and development of AS, remain unknown. Thus, the present study aimed to determine the proinflammatory roles of the oxLDL/β2GPI/anti-β2GPI Ab complex in human umbilical vein endothelial cells (HUVECs) in an attempt to determine the underlying mechanism. Reverse transcription-quantitative PCR, enzymy-linked immunosorbent assay, western blotting and immunofluorescence staining were performed to detect the expressions of inflammation related factors and adhesion molecules. Monocyte-binding assay was used to investigate the effects of oxLDL/β2GPI/anti-β2GPI Ab complex on monocyte adhesion to endothelial cells. The results demonstrated that the oxLDL/β2GPI/anti-β2GPI Ab complex upregulated the expression of Toll-like receptor (TLR)4 and the levels of NF-κB phosphorylation in HUVECs, and subsequently enhanced the expression levels of inflammatory cytokines, including TNF-α, IL-1β and IL-6, as well as those of adhesion molecules, such as intercellular adhesion molecule 1 and vascular adhesion molecule 1. In addition, the complex facilitated the recruitment of monocytes by promoting the secretion of monocyte chemotactic protein 1 in HUVECs. Notably, the described effects of the oxLDL/β2GPI/anti-β2GPI Ab complex in HUVECs were abolished by either TLR4 or NF-κB blockade. In conclusion, these findings suggested that the oxLDL/β2GPI/anti-β2GPI Ab complex may induce a hyper-inflammatory state in endothelial cells by promoting the secretion of proinflammatory cytokines and monocyte recruitment, which was discovered to be largely dependent on the TLR4/NK-κB signaling pathway.
Collapse
Affiliation(s)
- Guiting Zhang
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Qianqian Cai
- Department of Laboratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China
| | - Hong Zhou
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Chao He
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Yudan Chen
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Peng Zhang
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Ting Wang
- Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Liangjie Xu
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| | - Jinchuan Yan
- Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China
| |
Collapse
|
|
38
|
Kamperidis N, Kamperidis V, Zegkos T, Kostourou I, Nikolaidou O, Arebi N, Karvounis H. Atherosclerosis and Inflammatory Bowel Disease-Shared Pathogenesis and Implications for Treatment. Angiology 2020; 72:303-314. [PMID: 33601945 DOI: 10.1177/0003319720974552] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Atherosclerosis and inflammatory bowel disease (IBD) are often regarded as 2 distinct entities. The commonest manifestation of atherosclerosis is ischemic heart disease (IHD), and an association between IHD and IBD has been reported. Atherosclerosis and IBD share common pathophysiological mechanisms in terms of their genetics, immunology, and contributing environmental factors. Factors associated with atherosclerosis are implicated in the development of IBD and vice versa. Therefore, treatments targeting the common pathophysiology pathways may be effective in both conditions. The current review considers the pathophysiological pathways that are shared between the 2 conditions and discusses the implications for treatment and research.
Collapse
Affiliation(s)
- Nikolaos Kamperidis
- 3749St Mark's Hospital, Harrow, London, United Kingdom.,* Nikolaos Kamperidis and Vasileios Kamperidis are sharing first authorship
| | - Vasileios Kamperidis
- 1st Cardiology Department, 37788AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.,* Nikolaos Kamperidis and Vasileios Kamperidis are sharing first authorship
| | - Thomas Zegkos
- 1st Cardiology Department, 37788AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Olga Nikolaidou
- Radiology Department, Pananikolaou General Hospital, Thessaloniki, Greece
| | - Naila Arebi
- 3749St Mark's Hospital, Harrow, London, United Kingdom
| | - Haralambos Karvounis
- 1st Cardiology Department, 37788AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
39
|
Li Z, Qiao L, Yun X, Du F, Xing S, Yang M. Increased risk of ischemic heart disease and diabetes in inflammatory bowel disease. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 59:117-124. [PMID: 33233007 DOI: 10.1055/a-1283-6966] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Previous studies showed inconsistent results regarding associations between inflammatory bowel disease (IBD) and risk of ischemic heart disease (IHD) and diabetes. The present study aimed to make a meta-analysis to assess the risk of IHD and diabetes in IBD. METHODS We searched for articles published before February 2020 in the databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed odds ratio (OR) or relative risk (RR) and 95 % confidence intervals (CI) regarding the association between IBD and risk of IHD or diabetes by using STATA 13.0 software. RESULTS The present meta-analysis showed that IBD was associated with higher risk of IHD (OR/RR = 1.26, 95 % CI 1.20 to 1.32, I2 = 88.3 %, p < 0.0001). Additionally, both ulcerative colitis (UC) and Crohn's disease (CD) were associated with higher risk of IHD (UC: OR/RR = 1.19, 95 % CI 1.13 to 1.26, I2 = 65.6 %, p = 0.001; CD: OR/RR = 1.33, 95 % CI 1.17 to 1.51, I2 = 89.5 %, p < 0.0001). The study showed that IBD was associated with elevated risk of diabetes (OR/RR = 1.26, 95 % CI 1.03 to 1.53, I2 = 92.1 %, I2 = 92.1 %, p < 0.0001). Additionally, both UC and CD were associated with higher risk of diabetes (UC: OR/RR = 1.33, 95 % CI 1.03 to 1.71, I2 = 93.8 %, p < 0.0001; CD: OR/RR = 1.39, 95 % CI 1.10 to 1.76, I2 = 76.7 %, p = 0.002). CONCLUSION In conclusion, patients with IBD are at increased risk of IHD and diabetes. Thus, regular monitoring of biomarkers of IHD and blood glucose levels should be considered for the early detection of IHD and diabetes in IBD patients.
Collapse
Affiliation(s)
- Zhihui Li
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| | - Lili Qiao
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| | - Xiaojing Yun
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| | - Fangjuan Du
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| | - Shilei Xing
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| | - Maowu Yang
- Department of Gastroenterology, The Second People's Hospital of Liaocheng, the Second Hospital of Liaocheng affiliated to Shandong First Medical University, Liaocheng, Shandong Province, China
| |
Collapse
|
|
40
|
miR-4286/TGF-β1/Smad3-Negative Feedback Loop Ameliorated Vascular Endothelial Cell Damage by Attenuating Apoptosis and Inflammatory Response. J Cardiovasc Pharmacol 2020; 75:446-454. [PMID: 32141990 DOI: 10.1097/fjc.0000000000000813] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Atherosclerosis (AS), known as the chronic inflammatory disease, results from the dysfunction of vascular endothelial cells (VECs). Transforming growth factor-β1 (TGF-β1) has been reported to be induced by oxidized low-density lipoprotein (ox-LDL) and contribute to AS-related vascular endothelial cell damage. This work planned to study the mechanism of TGF-β1 in vascular endothelial cell damage. We found that TGF-β1 was activated by ox-LDL in human umbilical vascular endothelial cells (HUVECs). Silence of TGF-β1 reversed the inductive effect of ox-LDL on apoptosis and inflammatory response of HUVECs. Mechanistically, microRNA-4286 (miR-4286) targeted and inhibited TGF-β1 to inhibit Smad3, and Smad3 bound to the promoter of miR-4286 to repress its transcription. Rescue assays indicated that miR-4286 ameliorated the ox-LDL-induced apoptosis and inflammatory response through inhibiting TGF-β1. In conclusion, our study first demonstrated that miR-4286/TGF-β1/Smad3-negative feedback loop ameliorated vascular endothelial cell damage by attenuating apoptosis and inflammatory response, providing new thoughts for promoting the treatment of AS.
Collapse
|
|
41
|
Watad A, McGonagle D, Bragazzi NL, Damiani G, Comaneshter D, Lidar M, Cohen AD, Amital H. Systemic sclerosis is an independent risk factor for ischemic heart disease, especially in patients carrying certain antiphospholipid antibodies: A large cross-sectional study. Eur J Intern Med 2020; 81:44-49. [PMID: 32620499 DOI: 10.1016/j.ejim.2020.06.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/05/2020] [Accepted: 06/25/2020] [Indexed: 11/18/2022]
Abstract
BACKGROUND A higher prevalence of ischemic heart disease (IHD) in patients with systemic sclerosis (SSc) was reported. However, contrasting findings were published concerning the role of SSc-related autoantibodies in IHD risk which remains controversial. The current study explored the link between SSc and IHD, impact of putative links on SSc mortality and the role of SSc-related and antiphospholipid autoantibodies in disease associated IHD. METHODS A large cohort study utilising the Clalit-Health-Service (CHS) database was conducted on 2431 SSc patients and 12,710 age- and sex matched controls. The proportion of IHD was compared between patients diagnosed with SSc and age- and gender-matched controls. The role of SSc-linked and antiphospholipid autoantibodies in disease associated IHD was assessed. RESULTS The prevalence rate of IHD was significantly higher in SSc than controls (20.4% vs 15.0%, p <0.001). At the multivariate analysis, SSc was an independent predictor of IHD with an OR of 1.91 (95%CI 1.57-2.31, p < 0.0001). SSc patients with IHD had a higher mortality rate with an HR of 2.67 (95%CI 2.03-3.53, p < 0.0001) than those without IHD. In SSc patients positivity for anti-beta2GPI (IgM-isotype) or anti-cardiolipin (aCL) (IgA-isotype) represented a risk factor for IHD with an OR 1.89 (95% 1.04-3.45, p = 0.0369) and OR of 3.72 (95% 1.25-11.11, p = 0.0184), respectively. CONCLUSIONS Patients with SSc are at higher risk for developing IHD with an additional risk for the latter in those positive for aCL or anti-beta2GPI. A high degree of suspicion is needed during routine patient follow-up and pre-emptive screening should be considered.
Collapse
Affiliation(s)
- Abdulla Watad
- Department of Medicine 'B', The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Rheumatology Unit, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel; Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK.
| | - Dennis McGonagle
- Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK
| | - Nicola L Bragazzi
- Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, Canada
| | - Giovanni Damiani
- Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy; Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Doron Comaneshter
- Chief Physician's Office, Faculty of Health Sciences, Clalit Health Services Tel Aviv, Israel
| | - Merav Lidar
- Rheumatology Unit, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel
| | - Arnon D Cohen
- Chief Physician's Office, Faculty of Health Sciences, Clalit Health Services Tel Aviv, Israel; Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
| | - Howard Amital
- Department of Medicine 'B', The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Rheumatology Unit, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel
| |
Collapse
|
|
42
|
Wei X, Valenzuela NM, Rossetti M, Sosa RA, Nevarez-Mejia J, Fishbein GA, Mulder A, Dhar J, Keslar KS, Baldwin WM, Fairchild RL, Hou J, Reed EF. Antibody-induced vascular inflammation skews infiltrating macrophages to a novel remodeling phenotype in a model of transplant rejection. Am J Transplant 2020; 20:2686-2702. [PMID: 32320528 PMCID: PMC7529968 DOI: 10.1111/ajt.15934] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 03/15/2020] [Accepted: 04/07/2020] [Indexed: 01/25/2023]
Abstract
HLA donor-specific antibodies (DSAs) binding to vascular endothelial cells of the allograft trigger inflammation, vessel injury, and antibody-mediated rejection (AMR). Accumulation of intragraft-recipient macrophages is a histological characteristic of AMR, which portends worse outcome. HLA class I (HLA I) DSAs enhance monocyte recruitment by activating endothelial cells and engaging FcγRs, but the DSA-activated donor endothelial influence on macrophage differentiation is unknown. In this study, we explored the consequence of DSA-activated endothelium on infiltrating monocyte differentiation. Here we show that cardiac allografts from murine recipients treated with MHC I DSA upregulated genes related to monocyte transmigration and Fc receptor stimulation. Human monocytes co-cultured with HLA I IgG-stimulated primary human endothelium promoted monocyte differentiation into CD68+ CD206+ CD163+ macrophages (M(HLA I IgG)), whereas HLA I F(ab')2 stimulated endothelium solely induced higher CD206 (M(HLA I F(ab')2 )). Both macrophage subtypes exhibited significant changes in discrete cytokines/chemokines and unique gene expression profiles. Cross-comparison of gene transcripts between murine DSA-treated cardiac allografts and human co-cultured macrophages identified overlapping genes. These findings uncover the role of HLA I DSA-activated endothelium in monocyte differentiation, and point to a novel, remodeling phenotype of infiltrating macrophages that may contribute to vascular injury.
Collapse
Affiliation(s)
- Xuedong Wei
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Nicole M. Valenzuela
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Maura Rossetti
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Rebecca A. Sosa
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Jessica Nevarez-Mejia
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Gregory A. Fishbein
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Arend Mulder
- Department of Immunohaematology and Bloodtransfusion, Leiden University Medical Center, Leiden, Netherlands
| | - Jayeeta Dhar
- Lerner Research Institute and Transplant Center, Cleveland Clinic, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Karen S. Keslar
- Lerner Research Institute and Transplant Center, Cleveland Clinic, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - William M. Baldwin
- Lerner Research Institute and Transplant Center, Cleveland Clinic, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Robert L. Fairchild
- Lerner Research Institute and Transplant Center, Cleveland Clinic, Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Jianquan Hou
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Elaine F. Reed
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| |
Collapse
|
|
43
|
Qiu R, Zhou L, Ma Y, Zhou L, Liang T, Shi L, Long J, Yuan D. Regulatory T Cell Plasticity and Stability and Autoimmune Diseases. Clin Rev Allergy Immunol 2020; 58:52-70. [PMID: 30449014 DOI: 10.1007/s12016-018-8721-0] [Citation(s) in RCA: 80] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
CD4+CD25+ regulatory T cells (Tregs) are a class of CD4+ T cells with immunosuppressive functions that play a critical role in maintaining immune homeostasis. However, in certain disease settings, Tregs demonstrate plastic differentiation, and the stability of these Tregs, which is characterized by the stable expression or protective epigenetic modifications of the transcription factor Foxp3, becomes abnormal. Plastic Tregs have some features of helper T (Th) cells, such as the secretion of Th-related cytokines and the expression of specific transcription factors in Th cells, but also still retain the expression of Foxp3, a feature of Tregs. Although such Th-like Tregs can secrete pro-inflammatory cytokines, they still possess a strong ability to inhibit specific Th cell responses. Therefore, the plastic differentiation of Tregs not only increases the complexity of the immune circumstances under pathological conditions, especially autoimmune diseases, but also shows an association with changes in the stability of Tregs. The plastic differentiation and stability change of Tregs play vital roles in the progression of diseases. This review focuses on the phenotypic characteristics, functions, and formation conditions of several plastic Tregs and also summarizes the changes of Treg stability and their effects on inhibitory function. Additionally, the effects of Treg plasticity and stability on disease prognosis for several autoimmune diseases were also investigated in order to better understand the relationship between Tregs and autoimmune diseases.
Collapse
Affiliation(s)
- Runze Qiu
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Liyu Zhou
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Yuanjing Ma
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Lingling Zhou
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Tao Liang
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Le Shi
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China
| | - Jun Long
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China.
| | - Dongping Yuan
- School of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Xianlin Dadao 138, Nanjing, 210023, People's Republic of China.
| |
Collapse
|
|
44
|
Rezazadeh F, Moshaverinia M, Handjani F, Khoshkholgh F, Saki N, Heiran A. The Evaluation of Serum Lipids Profile in Patients with Pemphigus Vulgaris: A Case-Control Study. Malays J Med Sci 2020; 27:57-63. [PMID: 32788842 PMCID: PMC7409567 DOI: 10.21315/mjms2020.27.2.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 05/14/2019] [Indexed: 11/15/2022] Open
Abstract
Background Pemphigus vulgaris (PV) is a chronic autoimmune disease. Dyslipidemia, increased risk of atherosclerosis and higher cardiovascular morbidity, and mortality have been reported in several autoimmune conditions. It has been hypothesised that there might be an association between dyslipidemia and PV. Therefore, the objective of this study was to compare the serum lipid profile of patients with PV with healthy controls. Methods This case-control study was carried out on 113 patients with PV and 100 healthy controls. Total cholesterol, high-density lipoprotein (HDL) and triglycerides (TG) levels were measured and low-density lipoprotein (LDL), non-HDL cholesterol (non-HDL-C) and atherogenic index of plasma (AIP) were calculated. Chi-squared test and independent Student t-test (or their alternatives) were used for group comparison. Results The mean age and BMI of patients and controls were 47.7 ± 14.5 and 28 ± 6.2 and, 44.5 ± 18.5 and 25.5 ± 5.1, respectively. Total cholesterol, LDL, HDL, non-HDL-C and TG were statistically different between the two groups (P values < 0.001; < 0.001; < 0.001; < 0.001 and 0.021, respectively). However, AIP was not significantly different (P-value = 0.752). Conclusion The serum lipid profile was significantly higher in PV patients compared to healthy controls. Therefore, PV patients may be more prone to develop atherosclerosis and this finding can be important in the overall management of these patients.
Collapse
Affiliation(s)
- Fahimeh Rezazadeh
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Maryam Moshaverinia
- Department of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farhad Handjani
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Khoshkholgh
- Dentistry Student, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasrin Saki
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Dermatology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Heiran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| |
Collapse
|
|
45
|
Sałkowska A, Karaś K, Karwaciak I, Walczak-Drzewiecka A, Krawczyk M, Sobalska-Kwapis M, Dastych J, Ratajewski M. Identification of Novel Molecular Markers of Human Th17 Cells. Cells 2020; 9:cells9071611. [PMID: 32635226 PMCID: PMC7407666 DOI: 10.3390/cells9071611] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 12/15/2022] Open
Abstract
Th17 cells are important players in host defense against pathogens such as Staphylococcus aureus, Candida albicans, and Bacillus anthracis. Th17 cell-mediated inflammation, under certain conditions in which balance in the immune system is disrupted, is the underlying pathogenic mechanism of certain autoimmune disorders, e.g., rheumatoid arthritis, Graves' disease, multiple sclerosis, and psoriasis. In the present study, using transcriptomic profiling, we selected genes and analyzed the expression of these genes to find potential novel markers of Th17 lymphocytes. We found that APOD (apolipoprotein D); C1QL1 (complement component 1, Q subcomponent-like protein 1); and CTSL (cathepsin L) are expressed at significantly higher mRNA and protein levels in Th17 cells than in the Th1, Th2, and Treg subtypes. Interestingly, these genes and the proteins they encode are well associated with the function of Th17 cells, as these cells produce inflammation, which is linked with atherosclerosis and angiogenesis. Furthermore, we found that high expression of these genes in Th17 cells is associated with the acetylation of H2BK12 within their promoters. Thus, our results provide new information regarding this cell type. Based on these results, we also hope to better identify pathological conditions of clinical significance caused by Th17 cells.
Collapse
Affiliation(s)
- Anna Sałkowska
- Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland; (A.S.); (K.K.)
| | - Kaja Karaś
- Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland; (A.S.); (K.K.)
| | - Iwona Karwaciak
- Laboratory of Transcriptional Regulation, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland;
| | - Aurelia Walczak-Drzewiecka
- Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland; (A.W.-D.); (J.D.)
| | | | - Marta Sobalska-Kwapis
- Biobank Lab, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland;
- BBMRI.pl Consortium, 54-066 Wroclaw, Poland
| | - Jarosław Dastych
- Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland; (A.W.-D.); (J.D.)
| | - Marcin Ratajewski
- Laboratory of Epigenetics, Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland; (A.S.); (K.K.)
- Correspondence: ; Tel.: +48-42-209-33-89
| |
Collapse
|
|
46
|
Kim HJ, Kang T, Kang MJ, Ahn HS, Sohn SY. Incidence and Mortality of Myocardial Infarction and Stroke in Patients with Hyperthyroidism: A Nationwide Cohort Study in Korea. Thyroid 2020; 30:955-965. [PMID: 32093587 DOI: 10.1089/thy.2019.0543] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Background: Hyperthyroidism is associated with various cardiovascular risk factors. However, the relationship between hyperthyroidism and myocardial infarction (MI) or stroke has not been fully elucidated; only a few studies have investigated the association of hyperthyroidism with survival after MI or stroke. Methods: We included 59,021 hyperthyroid patients and a control cohort with 1,180,420 age- and sex-matched subjects from the Korean National Health Insurance database. Blood pressure, body mass index (BMI), glucose and cholesterol levels, and smoking history were obtained during National Health screening examination. We compared the incidence of MI, stroke, and survival after cardiovascular events between subjects with hyperthyroidism and the control cohort. Results: Subjects with hyperthyroidism had higher blood pressure, fasting glucose, and smoking rate, but lower cholesterol levels and a lower obesity rate compared with the control cohort. After adjusting these differences, as well as atrial fibrillation, hyperthyroidism was associated with increased risk of MI and ischemic stroke. Adjusted hazard ratios (HRs) for MI and ischemic stroke with hyperthyroidism was 1.16 [95% confidence interval, CI 1.03-1.30] and 1.12 [CI 1.04-1.20], respectively. In age-, sex-, and BMI-stratified analyses, an increased risk of MI and ischemic stroke remained significant in females, the older age group (≥50 years), and nonobese subjects (BMI <25 kg/m2), but not in males, the younger age group (<50 years), and obese subjects (BMI ≥25 kg/m2). The risk of hemorrhagic stroke was not different between subjects with hyperthyroidism and controls. Adjusted HRs for mortality in subjects with hyperthyroidism who developed MI, ischemic stroke, and hemorrhagic stroke were 1.11 ([CI 0.86-1.43], p = 0.44), 0.89 ([CI 0.75-1.05], p = 0.16), and 1.13 ([CI 0.88-1.47], p = 0.34), respectively. Conclusions: Hyperthyroidism is associated with increased risk of MI and ischemic stroke, independent of cardiovascular risk factors. This association is prominent in subjects with age ≥50 years, in females, and in the nonobese group. Hyperthyroidism did not significantly affect the mortality secondary to cardiovascular events.
Collapse
Affiliation(s)
- Hyun Jung Kim
- Department of Preventive Medicine, College of Medicine; Graduate School; Korea University, Seoul, Republic of Korea
| | - Taeuk Kang
- National Health Institute Service, Health Insurance Policy Research Institute, Wonju, Republic of Korea
| | - Min Ji Kang
- Department of Public Health, Graduate School; Korea University, Seoul, Republic of Korea
| | - Hyeong Sik Ahn
- Department of Preventive Medicine, College of Medicine; Graduate School; Korea University, Seoul, Republic of Korea
| | - Seo Young Sohn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Republic of Korea
| |
Collapse
|
|
47
|
Mohamed R, El-Bassyouni HT, Hasan Elwan S, Youness E, Soliman DR, M. Shehata G, Zaki ME. Carotid intima-media thickness, lipid profile, serum amyloid A and vitamin D status in children with familial Mediterranean fever. THE EGYPTIAN RHEUMATOLOGIST 2020. [DOI: 10.1016/j.ejr.2020.05.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
48
|
Aspirin enhances regulatory functional activities of monocytes and downregulates CD16 and CD40 expression in myocardial infarction autoinflammatory disease. Int Immunopharmacol 2020; 83:106349. [DOI: 10.1016/j.intimp.2020.106349] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Revised: 02/20/2020] [Accepted: 02/24/2020] [Indexed: 12/14/2022]
|
|
49
|
Liu S, Zhong Z, Zhong W, Weng R, Liu J, Gu X, Chen Y. Comprehensive analysis of T-cell receptor repertoire in patients with acute coronary syndrome by high-throughput sequencing. BMC Cardiovasc Disord 2020; 20:253. [PMID: 32460698 PMCID: PMC7254720 DOI: 10.1186/s12872-020-01538-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 05/18/2020] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND This study aims to investigate the T-cell receptor (TCR) repertoire in patients with acute coronary syndrome (ACS). METHODS The TCR repertoires of 9 unstable angina patients (UA), 14 acute myocardial infarction patients (AMI) and 9 normal coronary artery (NCA) patients were profiled using high-throughput sequencing (HTS). The clonal diversity of the TCR repertoires in different groups was analyzed, as well as the frequencies of variable (V), diversity (D) and joining(J) gene segments. RESULTS ACS patients including UA and AMI, showed reduced TCRβ diversity than NCA patients. ACS patients presented higher levels of clonal expansion. The clonotype overlap of complementarity determining region 3(CDR3) was significantly varied between different groups. A total of 10 V genes and 1 J gene were differently utilized between ACS and NCA patients. We identified some shared CDR3 amino acid sequences that were presented in ACS but not in NCA patients. CONCLUSIONS This study revealed the distinct TCR repertoires in patients with ACS and demonstrated the presence of disease associated T-cell clonotypes. These findings suggested a role of T cells in ACS and provided a new way to explore the mechanisms of ACS.
Collapse
Affiliation(s)
- Sudong Liu
- Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China. .,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China.
| | - Zhixiong Zhong
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizho, 514031, P. R. China.,Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, P. R. China
| | - Wei Zhong
- Center for Precision Medicine, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizho, 514031, P. R. China.,Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, 514031, P. R. China
| | - Ruiqiang Weng
- Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China
| | - Jing Liu
- Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China
| | - Xiaodong Gu
- Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China
| | - Yongyu Chen
- Clinical Core Laboratory, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, 514031, P. R. China
| |
Collapse
|
|
50
|
Splitthoff P, Rasbach E, Neudert P, Bonaterra GA, Schwarz A, Mey L, Schwarzbach H, Eiden LE, Weihe E, Kinscherf R. PAC1 deficiency attenuates progression of atherosclerosis in ApoE deficient mice under cholesterol-enriched diet. Immunobiology 2020; 225:151930. [PMID: 32173151 PMCID: PMC9741700 DOI: 10.1016/j.imbio.2020.151930] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 02/27/2020] [Accepted: 02/28/2020] [Indexed: 12/14/2022]
Abstract
The neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is vasoactive and cytoprotective and exerts immunoregulatory functions throughout the nervous, neuroendocrine cardiovascular and immune systems in health and disease. PACAP mainly acts through PAC1 receptor signaling in neuronal communication, but the role of PAC1 in immune regulation of atherosclerosis is not known. Here, we generated PAC1-/-/ApoE-/- mice to test, whether PAC1-/- influences plasma cholesterol-/triglyceride levels and/or atherogenesis in the brachiocephalic trunk (BT) seen in ApoE-/- mice, under standard chow (SC) or cholesterol-enriched diet (CED). Furthermore, the effect of PAC1-/-, on inflammatory, autophagy-, apoptosis- and necroptosis-relevant proteins in atherosclerotic plaques was determined. In plaques of PAC1-/-/ApoE-/- mice fed a SC, the immunoreactivity for apoptotic, autophagic, necroptotic and proinflammatory proteins was increased, however, proliferation was unaffected. Interestingly, without affecting hyperlipidemia, PAC1-/- in ApoE-/- mice remarkably reduced CED-induced lumen stenosis seen in ApoE-/- mice. Thus, PAC1-/- allows unchecked inflammation, necroptosis and decreased proliferation during SC, apparently priming the BT to develop reduced atheroma under subsequent CED. Remarkably, no differences in inflammation/necroptosis signatures in the atheroma under CED between PAC1-/-/ApoE-/- and ApoE-/- mice were observed. These data indicate that selective PAC1 antagonists should offer potential as a novel class of atheroprotective therapeutics, especially during hypercholesterolemia.
Collapse
Affiliation(s)
- Paul Splitthoff
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Erik Rasbach
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Philip Neudert
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Gabriel A. Bonaterra
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany,Corresponding author at: Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35032, Marburg, Germany., (G.A. Bonaterra)
| | - Anja Schwarz
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Lilli Mey
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Hans Schwarzbach
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Lee E. Eiden
- Section on Molecular Neuroscience, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health Intramural Research Program, Bethesda, 20814, Maryland, USA
| | - Eberhard Weihe
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| | - Ralf Kinscherf
- Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Medical Faculty, Philipps-University of Marburg, Robert-Koch-Str. 8, 35037, Marburg, Germany
| |
Collapse
|