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1
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Kim D, Ansari MM, Ghosh M, Heo Y, Choi KC, Son YO. Implications of obesity-mediated cellular dysfunction and adipocytokine signaling pathways in the pathogenesis of osteoarthritis. Mol Aspects Med 2025; 103:101361. [PMID: 40156972 DOI: 10.1016/j.mam.2025.101361] [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: 11/22/2024] [Revised: 03/17/2025] [Accepted: 03/25/2025] [Indexed: 04/01/2025]
Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone sclerosis, and chronic low-grade inflammation. Aging and injury play key roles in OA pathogenesis by triggering the release of proinflammatory factors from adipose tissue and other sources. Obesity and aging impair the function of endoplasmic reticulum (ER) chaperones, leading to ER stress, protein misfolding, and cellular apoptosis. Obesity also induces mitochondrial dysfunction in OA through oxidative stress and disrupts mitochondrial dynamics, exacerbating chondrocyte damage. These factors contribute to inflammation, matrix imbalance, and chondrocyte apoptosis. Adipocytes, the primary source of adipokines, release inflammatory mediators that affect joint cells. Several adipocytokines have a central role in the regulation of many aspects of inflammation. Adiponectin and leptin are the two most abundant adipocytokines that are strongly associated with OA progression. This literature review suggests that adipokines activate many signaling pathways to exert downstream effects and play significant roles in obesity-induced OA. Understanding this rapidly growing family of mainly adipocyte-derived mediators and obesity-mediated cellular dysfunction may be important in the development of new therapies for obesity-associated OA management.
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Affiliation(s)
- Dahye Kim
- Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Wanju, 55365, Republic of Korea.
| | - Md Meraj Ansari
- Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life, Sciences Jeju National University, Jeju-si, 63243, Republic of Korea; Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju-si, 63243, Republic of Korea.
| | - Mrinmoy Ghosh
- Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life, Sciences Jeju National University, Jeju-si, 63243, Republic of Korea.
| | - Yunji Heo
- Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life, Sciences Jeju National University, Jeju-si, 63243, Republic of Korea.
| | - Ki-Choon Choi
- Grassland and Forage Division, Rural Development Administration, National Institute of Animal Science, Cheonan, 31000, Republic of Korea.
| | - Young-Ok Son
- Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life, Sciences Jeju National University, Jeju-si, 63243, Republic of Korea; Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju-si, 63243, Republic of Korea; Bio-Health Materials Core-Facility Center, Jeju National University, Jeju-si, 63243, Republic of Korea; Practical Translational Research Center, Jeju National University, Jeju, 63243, Republic of Korea.
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2
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Janssen-Telders C, Eringa EC, de Groot JR, de Man FS, Handoko ML. The role of epicardial adipose tissue remodelling in heart failure with preserved ejection fraction. Cardiovasc Res 2025:cvaf056. [PMID: 40238568 DOI: 10.1093/cvr/cvaf056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/12/2024] [Accepted: 01/22/2025] [Indexed: 04/18/2025] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a growing global health problem characterized by high morbidity and mortality, with limited effective therapies available. Obesity significantly influences haemodynamic and structural changes in the myocardium and vasculature, primarily through the accumulation and action of visceral adipose tissue. Particularly, epicardial adipose tissue (EAT) contributes to HFpEF through inflammation and lipotoxic infiltration of the myocardium. However, the precise signalling pathways leading to diastolic stiffness in HFpEF require further elucidation. This review explores the dynamic role of EAT in health and disease. Drawing upon insights from studies in other conditions, we discuss potential EAT-mediated inflammatory pathways in HFpEF and how they may contribute to functional and structural myocardial and endothelial derangements, including intramyocardial lipid infiltration, fibrosis, endothelial dysfunction, cardiomyocyte stiffening, and left ventricular hypertrophy. Lastly, we propose potential targets for novel therapeutic avenues.
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Affiliation(s)
- Carolina Janssen-Telders
- Department of Cardiology Amsterdam UMC, Heart Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands
| | - Etto C Eringa
- Amsterdam Cardiovascular Sciences, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands
- Department of Physiology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht UMC, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
| | - Joris R de Groot
- Department of Cardiology Amsterdam UMC, Heart Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Amsterdam Cardiovascular Sciences, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands
| | - Frances S de Man
- Amsterdam Cardiovascular Sciences, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht UMC, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
| | - M Louis Handoko
- Department of Cardiology Amsterdam UMC, Heart Centre, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Department of Pulmonology, Amsterdam UMC, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
- Department of Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
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3
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Masset C, Drillaud N, Ternisien C, Degauque N, Gerard N, Bruneau S, Branchereau J, Blancho G, Mesnard B, Brouard S, Giral M, Cantarovich D, Dantal J. The concept of immunothrombosis in pancreas transplantation. Am J Transplant 2025; 25:650-668. [PMID: 39709128 DOI: 10.1016/j.ajt.2024.11.025] [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: 08/09/2024] [Revised: 11/06/2024] [Accepted: 11/23/2024] [Indexed: 12/23/2024]
Abstract
Early failure of a pancreatic allograft due to complete thrombosis has an incidence of approximately 10% and is the main cause of comorbidity in pancreas transplantation. Although several risk factors have been identified, the exact mechanisms leading to this serious complication are still unclear. In this review, we define the roles of the individual components involved during sterile immunothrombosis-namely endothelial cells, platelets, and innate immune cells. Further, we review the published evidence linking the main risk factors for pancreatic thrombosis to cellular activation and vascular modifications. We also explore the unique features of the pancreas itself: the vessel endothelium, specific vascularization, and relationship to other organs-notably the spleen and adipose tissue. Finally, we summarize the therapeutic possibilities for the prevention of pancreatic thrombosis depending on the different mechanisms such as anticoagulation, anti-inflammatory molecules, endothelium protectors, antagonism of damage-associated molecular patterns, and use of machine perfusion.
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Affiliation(s)
- Christophe Masset
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
| | - Nicolas Drillaud
- Laboratory of Hemostasis, Nantes University Hospital, Nantes, France
| | | | - Nicolas Degauque
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Nathalie Gerard
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Sarah Bruneau
- Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Julien Branchereau
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Gilles Blancho
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Benoit Mesnard
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Sophie Brouard
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Magali Giral
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Diego Cantarovich
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
| | - Jacques Dantal
- Institut de Transplantation-Urologie-Néphrologie (ITUN), Nantes University Hospital, Nantes, France; Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France
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Duan F, Wu J, Chang J, Peng H, Liu Z, Liu P, Han X, Sun T, Shang D, Yang Y, Li Z, Li P, Liu Y, Zhu Y, Lv Y, Guo X, Zhao Y, An Y. Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction. Differentiation 2025; 141:100832. [PMID: 39709882 DOI: 10.1016/j.diff.2024.100832] [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: 10/29/2024] [Revised: 12/15/2024] [Accepted: 12/16/2024] [Indexed: 12/24/2024]
Abstract
Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.
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Affiliation(s)
- Feiyi Duan
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiaoyan Wu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Jiayi Chang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Haoyuan Peng
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zitao Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengfei Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Xu Han
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Tiantian Sun
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Dandan Shang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yutian Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Zhihao Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Pengkun Li
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yixuan Liu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yonghao Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Yunzhi Lv
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; School of Stomatology, Henan University, Kaifeng, 475004, China
| | - Xiumei Guo
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Ying Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China
| | - Yang An
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, China; Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng Key Laboratory of Cell Signal Transduction, Henan University, Kaifeng, 475004, China.
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5
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Cai Y, Lv H, Yuan M, Wang J, Wu W, Fang X, Chen C, Mu J, Liu F, Gu X, Xie H, Liu Y, Xu H, Fan Y, Shen C, Ma X. Genome-wide association analysis of cystatin c and creatinine kidney function in Chinese women. BMC Med Genomics 2024; 17:272. [PMID: 39558362 PMCID: PMC11575226 DOI: 10.1186/s12920-024-02048-6] [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: 08/26/2024] [Accepted: 11/07/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population. METHODS By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis. RESULT One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2). CONCLUSION We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD.
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Affiliation(s)
- Yang Cai
- College of Public Health, Southwest Medical University, Luzhou, Sichuan, China
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hongyao Lv
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Meng Yuan
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jiao Wang
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Wenhui Wu
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiaoyu Fang
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China
| | - Changying Chen
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jialing Mu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Fangyuan Liu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Xincheng Gu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Hankun Xie
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Yu Liu
- Institute for the prevention and control of chronic non-communicable diseases, Center for Disease Control and Prevention of Jurong City, Jurong, China
| | - Haifeng Xu
- Institute for the prevention and control of chronic non-communicable diseases, Center for Disease Control and Prevention of Jurong City, Jurong, China
| | - Yao Fan
- Department of Clinical Epidemiology, Geriatric Hospital of Nanjing Medical University, Nanjing, China
| | - Chong Shen
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
| | - Xiangyu Ma
- College of Public Health, Southwest Medical University, Luzhou, Sichuan, China.
- Department of Epidemiology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, China.
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Miracle CE, McCallister CL, Egleton RD, Salisbury TB. Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer. Biochem Biophys Res Commun 2024; 733:150437. [PMID: 39074412 PMCID: PMC11455618 DOI: 10.1016/j.bbrc.2024.150437] [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: 05/10/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 07/31/2024]
Abstract
Obesity is associated with an increased risk for 13 different cancers. The increased risk for cancer in obesity is mediated by obesity-associated changes in the immune system. Obesity has distinct effects on different types of inflammation that are tied to tumorigenesis. For example, obesity promotes chronic inflammation in adipose tissue that is tumor-promoting in peripheral tissues. Conversely, obesity inhibits acute inflammation that rejects tumors. Obesity therefore promotes cancer by differentially regulating chronic versus acute inflammation. Given that obesity is chronic, the initial inflammation in adipose tissue will lead to systemic inflammation that could induce compensatory anti-inflammatory reactions in peripheral tissues to suppress chronic inflammation. The overall effect of obesity in peripheral tissues is therefore dependent on the duration and severity of obesity. Adipose tissue is a complex tissue that is composed of many cell types in addition to adipocytes. Further, adipose tissue cellularity is different at different anatomical sites throughout the body. Consequently, the sensitivity of adipose tissue to obesity is dependent on the anatomical location of the adipose depot. For example, obesity induces more inflammation in visceral than subcutaneous adipose tissue. Based on these studies, the mechanisms by which obesity promotes tumorigenesis are multifactorial and immune cell type-specific. The objective of our paper is to discuss the cellular mechanisms by which obesity promotes tumorigenesis by regulating distinct types of inflammation in adipose tissue and the tumor microenvironment.
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Affiliation(s)
- Cora E Miracle
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Chelsea L McCallister
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Richard D Egleton
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
| | - Travis B Salisbury
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, 1 John Marshall Drive, Huntington, WV, 25755, USA.
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7
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Marina Arroyo M, Ramírez Gallegos I, López-González ÁA, Vicente-Herrero MT, Vallejos D, Sastre-Alzamora T, Ramírez Manent JI. Usefulness of the ECORE-BF Scale to Determine Atherogenic Risk in 386,924 Spanish Workers. Nutrients 2024; 16:2434. [PMID: 39125315 PMCID: PMC11314428 DOI: 10.3390/nu16152434] [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: 06/28/2024] [Revised: 07/19/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Cardiovascular diseases are the leading cause of death worldwide. Obesity and atherosclerosis are considered risk factors for this pathology. There are multiple methods to evaluate obesity, in the same way as there are different formulas to determine atherogenic risk. Since both pathologies are closely related, the objective of our work was to evaluate whether the ECORE-BF scale is capable of predicting atherogenic risk. METHODS Observational, descriptive, and cross-sectional study in which 386,924 workers from several autonomous communities in Spain participated. The association between the ECORE-BF scale and five atherogenic risk indices was evaluated. The relationship between variables was assessed using the chi-square test and Student's t test in independent samples. Multivariate analysis was performed with the multinomial logistic regression test, calculating the odds ratio and 95% confidence intervals, with the Hosmer-Lemeshow goodness-of-fit test. ROC curves established the cut-off points for moderate and high vascular age and determined the Youden index. RESULTS The mean values of the ECORE-BF scale were higher in individuals with atherogenic dyslipidemia and the lipid triad, as well as in those with elevated values of the three atherogenic indices studied, with p <0.001 in all cases. As atherogenic risk increased across the five evaluated scales, the prevalence of obesity also significantly increased, with p <0.001 in all cases. In the ROC curve analysis, the AUCs for atherogenic dyslipidemia and the lipid triad were above 0.75, indicating a good association between these scales and the ECORE-BF. Although the Youden indices were not exceedingly high, they were around 0.5. CONCLUSIONS There is a good association between atherogenic risk scales, atherogenic dyslipidemia, and lipid triad, and the ECORE-BF scale. The ECORE-BF scale can be a useful and quick tool to evaluate atherogenic risk in primary care and occupational medicine consultations without the need for blood tests.
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Affiliation(s)
- Marta Marina Arroyo
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
| | - Ignacio Ramírez Gallegos
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
| | - Ángel Arturo López-González
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
- Faculty of Dentistry, ADEMA University School, 07010 Palma, Balearic Islands, Spain
- Institut d’Investigació Sanitària de les Illes Balears (IDISBA), Health Research Institute of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
- Health Service of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
| | - María Teófila Vicente-Herrero
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
| | - Daniela Vallejos
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
| | - Tomás Sastre-Alzamora
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
| | - José Ignacio Ramírez Manent
- Research ADEMA SALUD Group, University Institute for Research in Health Sciences (IUNICS), 07010 Palma, Balearic Islands, Spain; (M.M.A.); (I.R.G.); (M.T.V.-H.); (D.V.); (T.S.-A.); (J.I.R.M.)
- Institut d’Investigació Sanitària de les Illes Balears (IDISBA), Health Research Institute of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
- Health Service of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
- Faculty of Medicine, University of the Balearic Islands, 07010 Palma, Balearic Islands, Spain
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Krauz K, Kempiński M, Jańczak P, Momot K, Zarębiński M, Poprawa I, Wojciechowska M. The Role of Epicardial Adipose Tissue in Acute Coronary Syndromes, Post-Infarct Remodeling and Cardiac Regeneration. Int J Mol Sci 2024; 25:3583. [PMID: 38612394 PMCID: PMC11011833 DOI: 10.3390/ijms25073583] [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: 02/15/2024] [Revised: 03/17/2024] [Accepted: 03/19/2024] [Indexed: 04/14/2024] Open
Abstract
Epicardial adipose tissue (EAT) is a fat deposit surrounding the heart and located under the visceral layer of the pericardium. Due to its unique features, the contribution of EAT to the pathogenesis of cardiovascular and metabolic disorders is extensively studied. Especially, EAT can be associated with the onset and development of coronary artery disease, myocardial infarction and post-infarct heart failure which all are significant problems for public health. In this article, we focus on the mechanisms of how EAT impacts acute coronary syndromes. Particular emphasis was placed on the role of inflammation and adipokines secreted by EAT. Moreover, we present how EAT affects the remodeling of the heart following myocardial infarction. We further review the role of EAT as a source of stem cells for cardiac regeneration. In addition, we describe the imaging assessment of EAT, its prognostic value, and its correlation with the clinical characteristics of patients.
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Affiliation(s)
- Kamil Krauz
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; (K.K.); (M.K.); (P.J.); (K.M.)
| | - Marcel Kempiński
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; (K.K.); (M.K.); (P.J.); (K.M.)
| | - Paweł Jańczak
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; (K.K.); (M.K.); (P.J.); (K.M.)
| | - Karol Momot
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; (K.K.); (M.K.); (P.J.); (K.M.)
| | - Maciej Zarębiński
- Department of Invasive Cardiology, Independent Public Specialist Western Hospital John Paul II, Lazarski University, Daleka 11, 05-825 Grodzisk Mazowiecki, Poland; (M.Z.); (I.P.)
| | - Izabela Poprawa
- Department of Invasive Cardiology, Independent Public Specialist Western Hospital John Paul II, Lazarski University, Daleka 11, 05-825 Grodzisk Mazowiecki, Poland; (M.Z.); (I.P.)
| | - Małgorzata Wojciechowska
- Chair and Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Banacha 1b, 02-097 Warsaw, Poland; (K.K.); (M.K.); (P.J.); (K.M.)
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9
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Pande S, Vary C, Yang X, Liaw L, Gower L, Friesel R, Prudovsky I, Ryzhov S. Endothelial IL17RD promotes Western diet-induced aortic myeloid cell infiltration. Biochem Biophys Res Commun 2024; 701:149552. [PMID: 38335918 PMCID: PMC10936543 DOI: 10.1016/j.bbrc.2024.149552] [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: 11/20/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/12/2024]
Abstract
The Interleukin-17 (IL17) family is a group of cytokines implicated in the etiology of several inflammatory diseases. Interleukin-17 receptor D (IL17RD), also known as Sef (similar expression to fibroblast growth factor) belonging to the family of IL17 receptors, has been shown to modulate IL17A-associated inflammatory phenotypes. The objective of this study was to test the hypothesis that IL17RD promotes endothelial cell activation and consequent leukocyte adhesion. We utilized primary human aortic endothelial cells and demonstrated that RNAi targeting of IL17RD suppressed transcript levels by 83 % compared to non-targeted controls. Further, RNAi knockdown of IL17RD decreased the adhesion of THP-1 monocytic cells onto a monolayer of aortic endothelial cells in response to IL17A. Additionally, we determined that IL17A did not significantly enhance the activation of canonical MAPK and NFκB pathways in endothelial cells, and further did not significantly affect the expression of VCAM-1 and ICAM-1 in aortic endothelial cells, which is contrary to previous findings. We also determined the functional relevance of our findings in vivo by comparing the expression of endothelial VCAM-1 and ICAM-1 and leukocyte infiltration in the aorta in Western diet-fed Il17rd null versus wild-type mice. Our results showed that although Il17rd null mice do not have significant alteration in aortic expression of VCAM-1 and ICAM-1 in endothelial cells, they exhibit decreased accumulation of proinflammatory monocytes and neutrophils, suggesting that endothelial IL17RD induced in vivo myeloid cell accumulation is not dependent on upregulation of VCAM-1 and ICAM-1 expression. We further performed proteomics analysis to identify potential molecular mediators of the IL17A/IL17RD signaling axis. Collectively, our results underscore a critical role for Il17rd in the regulation of aortic myeloid cell infiltration in the context of Western diet feeding.
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Affiliation(s)
- Shivangi Pande
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA
| | - Calvin Vary
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA
| | - Xuehui Yang
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA
| | - Lucy Liaw
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA
| | - Lindsey Gower
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA
| | - Robert Friesel
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA.
| | - Igor Prudovsky
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA.
| | - Sergey Ryzhov
- Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth, 81 Research Drive, Scarborough, ME, 04074, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, 04496, USA.
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10
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Wang P, Konja D, Singh S, Zhang B, Wang Y. Endothelial Senescence: From Macro- to Micro-Vasculature and Its Implications on Cardiovascular Health. Int J Mol Sci 2024; 25:1978. [PMID: 38396653 PMCID: PMC10889199 DOI: 10.3390/ijms25041978] [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: 12/27/2023] [Revised: 02/02/2024] [Accepted: 02/03/2024] [Indexed: 02/25/2024] Open
Abstract
Endothelial cells line at the most inner layer of blood vessels. They act to control hemostasis, arterial tone/reactivity, wound healing, tissue oxygen, and nutrient supply. With age, endothelial cells become senescent, characterized by reduced regeneration capacity, inflammation, and abnormal secretory profile. Endothelial senescence represents one of the earliest features of arterial ageing and contributes to many age-related diseases. Compared to those in arteries and veins, endothelial cells of the microcirculation exhibit a greater extent of heterogeneity. Microcirculatory endothelial senescence leads to a declined capillary density, reduced angiogenic potentials, decreased blood flow, impaired barrier properties, and hypoperfusion in a tissue or organ-dependent manner. The heterogeneous phenotypes of microvascular endothelial cells in a particular vascular bed and across different tissues remain largely unknown. Accordingly, the mechanisms underlying macro- and micro-vascular endothelial senescence vary in different pathophysiological conditions, thus offering specific target(s) for therapeutic development of senolytic drugs.
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Affiliation(s)
- Peichun Wang
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; (P.W.); (D.K.); (S.S.); (B.Z.)
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Daniels Konja
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; (P.W.); (D.K.); (S.S.); (B.Z.)
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Sandeep Singh
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; (P.W.); (D.K.); (S.S.); (B.Z.)
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Beijia Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; (P.W.); (D.K.); (S.S.); (B.Z.)
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Yu Wang
- State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China; (P.W.); (D.K.); (S.S.); (B.Z.)
- Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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11
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Srikanth M, Rasool M. Resistin - A Plausible Therapeutic Target in the Pathogenesis of Psoriasis. Immunol Invest 2024; 53:115-159. [PMID: 38054436 DOI: 10.1080/08820139.2023.2288836] [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] [Indexed: 12/07/2023]
Abstract
Resistin, a cytokine hormone predominantly secreted by adipose tissue, is elevated in various metabolic disorders such as obesity, type 2 diabetes, and cardiovascular disease. In addition to its involvement in metabolic regulation, resistin has been implicated in the pathogenesis of psoriasis, a chronic inflammatory skin disorder. Numerous studies have reported increased resistin levels in psoriatic skin lesions, suggesting a possible association between resistin and psoriasis. Recent studies have suggested the potential involvement of resistin in the development and progression of certain cancers. Resistin is overexpressed in breast, colorectal, and gastric cancers. This suggests that it may play a role in the development of these cancers, possibly by inducing inflammation and cell growth. The link between resistin and cancer raises the possibility of shared underlying mechanisms driving the pathogenesis of psoriasis. Chronic inflammation, one such mechanism, is a hallmark of psoriasis and cancer. Further research is needed to fully understand the relationship between resistin and psoriasis. Identifying potential therapeutic targets is crucial for effective management of psoriasis. By doing so, we may be able to develop more effective treatment options for individuals living with psoriasis and ultimately improve their quality of life. Ultimately, a more comprehensive understanding of the mechanisms underlying the impact of resistin on psoriasis is essential for advancing our knowledge and finding new ways to treat and manage this challenging condition.
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Affiliation(s)
- Manupati Srikanth
- Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, India
| | - Mahaboobkhan Rasool
- Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, India
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12
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Domingo E, Marques P, Francisco V, Piqueras L, Sanz MJ. Targeting systemic inflammation in metabolic disorders. A therapeutic candidate for the prevention of cardiovascular diseases? Pharmacol Res 2024; 200:107058. [PMID: 38218355 DOI: 10.1016/j.phrs.2024.107058] [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: 07/26/2023] [Revised: 12/11/2023] [Accepted: 01/03/2024] [Indexed: 01/15/2024]
Abstract
Cardiovascular disease (CVD) remains the leading cause of death and disability worldwide. While many factors can contribute to CVD, atherosclerosis is the cardinal underlying pathology, and its development is associated with several metabolic risk factors including dyslipidemia and obesity. Recent studies have definitively demonstrated a link between low-grade systemic inflammation and two relevant metabolic abnormalities: hypercholesterolemia and obesity. Interestingly, both metabolic disorders are also associated with endothelial dysfunction/activation, a proinflammatory and prothrombotic phenotype of the endothelium that involves leukocyte infiltration into the arterial wall, one of the earliest stages of atherogenesis. This article reviews the current literature on the intricate relationship between hypercholesterolemia and obesity and the associated systemic inflammation and endothelial dysfunction, and discusses the effectiveness of present, emerging and in-development pharmacological therapies used to treat these metabolic disorders with a focus on their effects on the associated systemic inflammatory state and cardiovascular risk.
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Affiliation(s)
- Elena Domingo
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain; Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Patrice Marques
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain; Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain
| | - Vera Francisco
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain; Endocrinology and Nutrition Service, University Clinic Hospital of Valencia, Valencia, Spain
| | - Laura Piqueras
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain; Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain; CIBERDEM, Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders, Carlos III Health Institute (ISCIII), Spain.
| | - Maria-Jesus Sanz
- Institute of Health Research INCLIVA, University Clinic Hospital of Valencia, Valencia, Spain; Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Valencia, Spain; CIBERDEM, Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders, Carlos III Health Institute (ISCIII), Spain.
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13
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Pezzino S, Luca T, Castorina M, Puleo S, Latteri S, Castorina S. Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines. Life (Basel) 2024; 14:93. [PMID: 38255708 PMCID: PMC10820028 DOI: 10.3390/life14010093] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/04/2024] [Accepted: 01/05/2024] [Indexed: 01/24/2024] Open
Abstract
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.
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Affiliation(s)
- Salvatore Pezzino
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Tonia Luca
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | | | - Stefano Puleo
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
| | - Sergio Castorina
- Mediterranean Foundation “GB Morgagni”, 95125 Catania, Italy (M.C.); (S.C.)
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy;
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14
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Nowicka B, Torres A, Polkowska I, Jackow-Nowicka J, Przewozny M, Jackow-Malinowska J. Concentrations of Selected Adipocytokines in the Blood Plasma in Proximal Suspensory Desmopathy of Horses, with a Focus on Their Physical Activity-A Pilot Study. Int J Mol Sci 2023; 25:205. [PMID: 38203376 PMCID: PMC10778773 DOI: 10.3390/ijms25010205] [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: 11/25/2023] [Revised: 12/17/2023] [Accepted: 12/20/2023] [Indexed: 01/12/2024] Open
Abstract
Chronic tendon and ligament diseases are commonly encountered in both athletic humans and animals, especially horses. Distal limb diseases, including suspensory ligament (SL) pathology due to anatomical, histological, and biomechanical properties, can be considered a model for tendon and ligament pathologies in humans. The appropriate selection of therapy is often crucial in optimising the healing process. One decisive factor influencing the possibility of returning to pre-disease training levels appears to be the utilisation of physical activity, including controlled movement, during the rehabilitation process. In the pathogenesis of musculoskeletal diseases and rehabilitation, adipocytokines play diverse roles. However, it is unclear what significance they hold in horses and in specific disease entities as well as the consequences of their mutual interactions. Recent studies indicate that in the pathogenesis of diseases with varied aetiologies in humans, their value varies at different stages, resulting in a diverse response to treatment. The results of this study demonstrate lower resistin concentrations in the venous blood plasma of horses with proximal suspensory desmopathy (PSD), while higher levels were observed in regularly trained and paddocked animals. The horses investigated in this study showed higher concentrations of resistin and IL-8, particularly in paddocked horses as well as in the working group of horses. The results suggest that these concentrations, including resistin in blood plasma, may be clinically significant. This attempt to explore the aetiopathogenesis of the processes occurring in the area of the proximal attachment of the suspensory ligament may optimise the procedures for the treatment and rehabilitation of horses.
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Affiliation(s)
- Beata Nowicka
- Department and Clinic of Animal Surgery, University of Life Sciences in Lublin, Głeboka 30, 20-612 Lublin, Poland;
| | - Anna Torres
- Department of Pediatric and Adolescent Gynecology, Medical University of Lublin, Chodzki 4, 20-094 Lublin, Poland;
| | - Izabela Polkowska
- Department and Clinic of Animal Surgery, University of Life Sciences in Lublin, Głeboka 30, 20-612 Lublin, Poland;
| | - Jagoda Jackow-Nowicka
- Department of General and Interventional Radiology and Neuroradiology, Wroclaw Medical University, ul. Borowska 213, 50-556 Wrocław, Poland
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15
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Hua K, Li T, He Y, Guan A, Chen L, Gao Y, Xu Q, Wang H, Luo R, Zhao L, Jin H. Resistin secreted by porcine alveolar macrophages leads to endothelial cell dysfunction during Haemophilus parasuis infection. Virulence 2023; 14:2171636. [PMID: 36694280 PMCID: PMC9928480 DOI: 10.1080/21505594.2023.2171636] [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] [Indexed: 01/26/2023] Open
Abstract
Haemophilus parasuis (H. parasuis) causes exudative inflammation, implying endothelial dysfunction during pathogen infection. However, so far, the molecular mechanism of endothelial dysfunction caused by H. parasuis has not been clarified. By using the transwell-based cell co-culture system, we demonstrate that knocking out resistin in porcine alveolar macrophages (PAMs) dramatically attenuated endothelial monolayer damage caused by H. parasuis. The resistin secreted by PAMs inhibited the expression of the tight junction proteins claudin-5 and occludin rather than the adherens junction protein VE-cadherin in co-cultured porcine aortic endothelial cells (PAECs). Furthermore, we demonstrate that resistin regulated claudin-5 and occludin expression and monolayer PAEC permeability in an LKB1/AMPK/mTOR pathway-dependent manner. Additionally, we reveal that the outer membrane lipoprotein gene lppA in H. parasuis induced resistin expression in PAMs, as deleting lppA reduced resistin expression in H. parasuis-infected PAMs, causing a significant change in LKB1/AMPK/mTOR pathway activity in co-cultured PAECs, thereby restoring tight junction protein levels and endothelial monolayer permeability. Thus, we postulate that the H. parasuis lppA gene enhances resistin production in PAMs, disrupting tight junctions in PAECs and causing endothelial barrier dysfunction. These findings elucidate the pathogenic mechanism of exudative inflammation caused by H. parasuis for the first time and provide a more profound angle of acute exudative inflammation caused by bacteria.
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Affiliation(s)
- Kexin Hua
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Tingting Li
- Department of Animal Disease Diagnosis, Hubei Animal Disease Prevention and Control Centre, Wuhan, China
| | - Yanling He
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Aohan Guan
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Liying Chen
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Yuan Gao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Qianshuan Xu
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Haoyu Wang
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Rui Luo
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Ling Zhao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China
| | - Hui Jin
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China,College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China,Hubei Provincial Key Laboratory of Preventive Veterinary Medicine, Huazhong Agricultural University, China,CONTACT Hui Jin
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16
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Al Zein M, Zein O, Diab R, Dimachkie L, Sahebkar A, Al-Asmakh M, Kobeissy F, Eid AH. Intermittent fasting favorably modulates adipokines and potentially attenuates atherosclerosis. Biochem Pharmacol 2023; 218:115876. [PMID: 37871879 DOI: 10.1016/j.bcp.2023.115876] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 10/19/2023] [Accepted: 10/20/2023] [Indexed: 10/25/2023]
Abstract
Adipose tissue is now recognized as an endocrine organ that secretes bioactive molecules called adipokines. These biomolecules regulate key physiological functions, including insulin sensitivity, energy metabolism, appetite regulation, endothelial function and immunity. Dysregulated secretion of adipokines is intimately associated with obesity, and translates into increased risk of obesity-related cardiovasculo-metabolic diseases. In particular, emerging evidence suggests that adipokine imbalance contributes to the pathogenesis of atherosclerosis. One of the promising diet regimens that is beneficial in the fight against obesity and cardiometabolic disorders is intermittent fasting (IF). Indeed, IF robustly suppresses inflammation, meditates weight loss and mitigates many aspects of the cardiometabolic syndrome. In this paper, we review the main adipokines and their role in atherosclerosis, which remains a major contributor to cardiovascular-associated morbidity and mortality. We further discuss how IF can be employed as an effective management modality for obesity-associated atherosclerosis. By exploring a plethora of the beneficial effects of IF, particularly on inflammatory markers, we present IF as a possible intervention to help prevent atherosclerosis.
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Affiliation(s)
- Mohammad Al Zein
- Faculty of Medical Sciences, Lebanese University, Hadath, Beirut, Lebanon
| | - Omar Zein
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Rawan Diab
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - Lina Dimachkie
- Faculty of Medicine, American University of Beirut, Beirut, Lebanon
| | - 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
| | - Maha Al-Asmakh
- Department of Biomedical Sciences, College of Health Sciences, QU Health, Qatar University, Doha, Qatar; Biomedical Research Center, Qatar University, Doha, Qatar
| | - Firas Kobeissy
- Department of Neurobiology and Neuroscience, Morehouse School of Medicine, Atlanta, GA, USA
| | - Ali H Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar.
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Hadate T, Kawamura R, Tabara Y, Maruyama K, Takakado M, Ikeda Y, Ohashi J, Takata Y, Saito I, Osawa H. Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study. J Hum Genet 2023; 68:745-750. [PMID: 37423942 DOI: 10.1038/s10038-023-01176-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 06/01/2023] [Accepted: 06/12/2023] [Indexed: 07/11/2023]
Abstract
Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.
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Affiliation(s)
- Toshimi Hadate
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Ryoichi Kawamura
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yasuharu Tabara
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Koutatsu Maruyama
- Department of Bioscience, Graduate School of Agriculture, Ehime University, Ehime, Japan
| | - Misaki Takakado
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yosuke Ikeda
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Jun Ohashi
- Department of Biological Sciences, Graduate School of Science, University of Tokyo, Tokyo, Japan
| | - Yasunori Takata
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Isao Saito
- Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Oita, Japan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, Japan.
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18
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Huber K, Szerenos E, Lewandowski D, Toczylowski K, Sulik A. The Role of Adipokines in the Pathologies of the Central Nervous System. Int J Mol Sci 2023; 24:14684. [PMID: 37834128 PMCID: PMC10572192 DOI: 10.3390/ijms241914684] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/24/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Adipokines are protein hormones secreted by adipose tissue in response to disruptions in physiological homeostasis within the body's systems. The regulatory functions of adipokines within the central nervous system (CNS) are multifaceted and intricate, and they have been identified in a number of pathologies. Therefore, specific adipokines have the potential to be used as biomarkers for screening purposes in neurological dysfunctions. The systematic review presented herein focuses on the analysis of the functions of various adipokines in the pathogenesis of CNS diseases. Thirteen proteins were selected for analysis through scientific databases. It was found that these proteins can be identified within the cerebrospinal fluid either by their ability to modify their molecular complex and cross the blood-brain barrier or by being endogenously produced within the CNS itself. As a result, this can correlate with their measurability during pathological processes, including Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, depression, or brain tumors.
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Affiliation(s)
| | | | | | - Kacper Toczylowski
- Department of Pediatric Infectious Diseases, Medical University of Bialystok, Waszyngtona 17, 15-274 Bialystok, Poland
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19
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Luo J, He Z, Li Q, Lv M, Cai Y, Ke W, Niu X, Zhang Z. Adipokines in atherosclerosis: unraveling complex roles. Front Cardiovasc Med 2023; 10:1235953. [PMID: 37645520 PMCID: PMC10461402 DOI: 10.3389/fcvm.2023.1235953] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 08/02/2023] [Indexed: 08/31/2023] Open
Abstract
Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.
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Affiliation(s)
- Jiaying Luo
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhiwei He
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Qingwen Li
- Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Mengna Lv
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Yuli Cai
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Ke
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xuan Niu
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zhaohui Zhang
- Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China
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20
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Garbuzova EV, Khudiakova AD, Shcherbakova LV, Kashtanova EV, Polonskaya YV, Stakhneva EM, Ragino YI. Associations of Adipocytokines and Early Renal Dysfunction in Young People on the Background of Dyslipidemia. J Pers Med 2023; 13:1238. [PMID: 37623488 PMCID: PMC10455902 DOI: 10.3390/jpm13081238] [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: 07/06/2023] [Revised: 07/28/2023] [Accepted: 08/05/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. MATERIALS AND METHODS A population study was conducted in IIPM-Branch of IC&G SB RAS, in 2013-2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. RESULTS Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. CONCLUSIONS In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction.
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Affiliation(s)
| | | | | | | | | | | | - Yulia I. Ragino
- Research Institute of Internal and Preventive Medicine–Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM—Branch of IC&G SB RAS), B. Bogatkova Str., 175/1, 630089 Novosibirsk, Russia; (E.V.G.); (A.D.K.); (L.V.S.); (E.V.K.); (Y.V.P.); (E.M.S.)
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21
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Khalaji A, Behnoush AH, Mohtasham Kia Y, Alehossein P, Bahiraie P. High circulating endocan in chronic kidney disease? A systematic review and meta-analysis. PLoS One 2023; 18:e0289710. [PMID: 37556458 PMCID: PMC10411816 DOI: 10.1371/journal.pone.0289710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 07/23/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is one of the leading causes of morbidity and mortality worldwide. Endothelial dysfunction has been suggested to be involved in the pathophysiology of CKD. Endocan, as an endothelial factor, has been shown to increase in several diseases. The current systematic review and meta-analysis was performed with the aim of determining the association between endocan levels and CKD. METHODS Four international databases, including PubMed, Embase, Scopus, and Web of Science were searched for relevant studies. Afterward, screening and extraction of data were performed. We conducted a random-effect meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) to compare circulating endocan levels between patients with CKD (including patients undergoing hemodialysis) and healthy controls. Subgroup analysis based on the specimen in which endocan was measured (serum or plasma) was also performed. RESULTS After screening by title/abstract and full-text review by the authors, 20 studies were included. Meta-analysis revealed that serum endocan is higher in CKD patients compared to healthy controls (SMD 1.34, 95% CI 0.20 to 2.48, p-value<0.01). This higher endocan level was also observed in the subgroup of studies that measured plasma endocan while this was not the case for the subgroup of studies assessing serum endocan. Meta-analysis was also performed for comparison of CKD patients without other comorbidities and healthy controls, which resulted in the same conclusion of higher endocan levels in patients with CKD (SMD 0.74, 95% CI 0.52 to 0.95, p-value<0.01). Moreover, endocan was associated with cardiovascular diseases in CKD. CONCLUSION Our study demonstrated that endocan is significantly increased in patients with CKD. This can have clinical implications as well as highlight the need for future research investigating the diagnostic and prognostic role of endocan in CKD.
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Affiliation(s)
- Amirmohammad Khalaji
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Population Sciences Institute, Non-Communicable Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Behnoush
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Population Sciences Institute, Non-Communicable Diseases Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Parsa Alehossein
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Pegah Bahiraie
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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22
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CHOI EW. Relationship between neutrophil gelatinase-associated lipocalin levels and disease parameters including clinicopathological parameters and various cytokine levels in systemic lupus erythematosus. J Vet Med Sci 2023; 85:601-608. [PMID: 37088550 PMCID: PMC10315541 DOI: 10.1292/jvms.23-0015] [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: 01/07/2023] [Accepted: 04/07/2023] [Indexed: 04/25/2023] Open
Abstract
Urine neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury and indicates tubular damage. Lupus nephritis-associated renal injury is characterized by damage to the glomeruli and tubular portions of the kidneys. Therefore, NGAL concentrations are expected to vary according to the severity of systemic lupus erythematosus (SLE). In this study, samples from (NZB × NZW) F1 mice at an advanced stage of SLE were used to determine whether serum and urine NGAL concentrations or the urine NGAL:creatinine (uNGAL/C) ratio can be used to reflect diet, disease state, and treatment efficacy. Additionally, the relationship between the levels of NGAL and various cytokines in the serum in SLE was evaluated. Mice were divided into the following four groups (n=15): CN, chow diet and no treatment (saline; intraperitonially injected [i.p.]; 200 μL/day); CP, chow diet and methylprednisolone (i.p.; 5 mg/kg/day); HN, high-fat diet and no treatment (saline [i.p.]; 200 μL/day); and HP, high-fat diet and methylprednisolone treatment (i.p.; 5 mg/kg/day) every day from 6 to 42 weeks of age. The serum and urine NGAL levels and uNGAL/C values were significantly lower in the CP group than those in the CN group. Further, serum NGAL concentration demonstrated a strong positive correlation with urine NGAL levels, uNGAL/C, urine protein concentrations, urine protein:creatinine ratio, and the expression of several cytokines associated with SLE pathogenesis (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and interferon-induced protein [IP]-10). These results suggest that NGAL has a strong positive correlation with the clinicopathological parameters and several key cytokines in SLE.
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Affiliation(s)
- Eun Wha CHOI
- Department of Veterinary Clinical Pathology, College of
Veterinary Medicine & Institute of Veterinary Science, Kangwon National University,
Gangwon-do, Republic of Korea
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23
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Vasamsetti SB, Natarajan N, Sadaf S, Florentin J, Dutta P. Regulation of cardiovascular health and disease by visceral adipose tissue-derived metabolic hormones. J Physiol 2023; 601:2099-2120. [PMID: 35661362 PMCID: PMC9722993 DOI: 10.1113/jp282728] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 05/04/2022] [Indexed: 11/08/2022] Open
Abstract
Visceral adipose tissue (VAT) is a metabolic organ known to regulate fat mass, and glucose and nutrient homeostasis. VAT is an active endocrine gland that synthesizes and secretes numerous bioactive mediators called 'adipocytokines/adipokines' into systemic circulation. These adipocytokines act on organs of metabolic importance like the liver and skeletal muscle. Multiple preclinical and in vitro studies showed strong evidence of the roles of adipocytokines in the regulation of metabolic disorders like diabetes, obesity and insulin resistance. Adipocytokines, such as adiponectin and omentin, are anti-inflammatory and have been shown to prevent atherogenesis by increasing nitric oxide (NO) production by the endothelium, suppressing endothelium-derived inflammation and decreasing foam cell formation. By inhibiting differentiation of vascular smooth muscle cells (VSMC) into osteoblasts, adiponectin and omentin prevent vascular calcification. On the other hand, adipocytokines like leptin and resistin induce inflammation and endothelial dysfunction that leads to vasoconstriction. By promoting VSMC migration and proliferation, extracellular matrix degradation and inflammatory polarization of macrophages, leptin and resistin increase the risk of atherosclerotic plaque vulnerability and rupture. Additionally, the plasma concentrations of these adipocytokines alter in ageing, rendering older humans vulnerable to cardiovascular disease. The disturbances in the normal physiological concentrations of these adipocytokines secreted by VAT under pathological conditions impede the normal functions of various organs and affect cardiovascular health. These adipokines could be used for both diagnostic and therapeutic purposes in cardiovascular disease.
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Affiliation(s)
- Sathish Babu Vasamsetti
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA 15213
- Pittsburgh VA Medical Center-University Drive, University Drive C, Pittsburgh, PA, USA
| | - Niranjana Natarajan
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA 15213
| | - Samreen Sadaf
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA 15213
- Pittsburgh VA Medical Center-University Drive, University Drive C, Pittsburgh, PA, USA
| | - Jonathan Florentin
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA 15213
| | - Partha Dutta
- Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA 15213
- Pittsburgh VA Medical Center-University Drive, University Drive C, Pittsburgh, PA, USA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA, 15213
- Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA, 15213
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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24
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Ahmed A, Bibi A, Valoti M, Fusi F. Perivascular Adipose Tissue and Vascular Smooth Muscle Tone: Friends or Foes? Cells 2023; 12:cells12081196. [PMID: 37190105 DOI: 10.3390/cells12081196] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 04/09/2023] [Accepted: 04/15/2023] [Indexed: 05/17/2023] Open
Abstract
Perivascular adipose tissue (PVAT) is a specialized type of adipose tissue that surrounds most mammalian blood vessels. PVAT is a metabolically active, endocrine organ capable of regulating blood vessel tone, endothelium function, vascular smooth muscle cell growth and proliferation, and contributing critically to cardiovascular disease onset and progression. In the context of vascular tone regulation, under physiological conditions, PVAT exerts a potent anticontractile effect by releasing a plethora of vasoactive substances, including NO, H2S, H2O2, prostacyclin, palmitic acid methyl ester, angiotensin 1-7, adiponectin, leptin, and omentin. However, under certain pathophysiological conditions, PVAT exerts pro-contractile effects by decreasing the production of anticontractile and increasing that of pro-contractile factors, including superoxide anion, angiotensin II, catecholamines, prostaglandins, chemerin, resistin, and visfatin. The present review discusses the regulatory effect of PVAT on vascular tone and the factors involved. In this scenario, dissecting the precise role of PVAT is a prerequisite to the development of PVAT-targeted therapies.
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Affiliation(s)
- Amer Ahmed
- Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
| | - Aasia Bibi
- Nanotechnology Institute, CNR-NANOTEC, Via Monteroni, 73100 Lecce, Italy
| | - Massimo Valoti
- Department of Life Sciences, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
| | - Fabio Fusi
- Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy
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25
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Romejko K, Rymarz A, Szamotulska K, Bartoszewicz Z, Rozmyslowicz T, Niemczyk S. Resistin Contribution to Cardiovascular Risk in Chronic Kidney Disease Male Patients. Cells 2023; 12:cells12070999. [PMID: 37048072 PMCID: PMC10093733 DOI: 10.3390/cells12070999] [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: 02/17/2023] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Resistin is a molecule that belongs to the Resistin-Like Molecules family (RELMs), the group of proteins taking part in inflammatory processes. Increased resistin concentrations are observed in cardiovascular complications. Resistin contributes to the onset of atherosclerosis and intensifies the atherosclerotic processes. The aim of this study was to investigate the relationship between resistin and cardiovascular (CV) risk in men with chronic kidney disease (CKD) not treated with dialysis. MATERIALS AND METHODS One hundred and forty-two men were included in the study: 99 men with eGFR lower than 60 mL/min/1.73 m2 and 43 men with eGFR ≥ 60 mL/min/1.73 m2. CV risk was assessed. Serum resistin, tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured among other biochemical parameters. RESULTS We observed that resistin concentrations were significantly higher in patients with CKD compared to individuals with eGFR ≥ 60 mL/min/1.73 m2 (p = 0.003). In CKD, after estimating the general linear model (GLM), we found that resistin is associated with CV risk (p = 0.026) and PAI-1 serum concentrations (0.012). The relationship of PAI-1 with resistin depends on the level of CV risk in CKD (p = 0.048). CONCLUSIONS Resistin concentrations rise with the increase of CV risk in CKD patients and thus resistin may contribute to the progression of cardiovascular risk in this group of patients. The relationship between resistin and CV risk is modified by PAI-1 concentrations.
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Affiliation(s)
- Katarzyna Romejko
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
| | - Aleksandra Rymarz
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
| | - Katarzyna Szamotulska
- Department of Epidemiology and Biostatistics, Institute of Mother and Child, 01-211 Warsaw, Poland
| | - Zbigniew Bartoszewicz
- Department of Internal Diseases and Endocrinology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Tomasz Rozmyslowicz
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Stanisław Niemczyk
- Department of Internal Diseases, Nephrology and Dialysis, Military Institute of Medicine-National Research Institute, 04-141 Warsaw, Poland
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26
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Gasbarrino K, Hafiane A, Gianopoulos I, Zheng H, Mantzoros CS, Daskalopoulou SS. Relationship between circulating adipokines and cholesterol efflux in subjects with severe carotid atherosclerosis. Metabolism 2023; 140:155381. [PMID: 36566801 DOI: 10.1016/j.metabol.2022.155381] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 12/02/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
AIMS Cholesterol efflux capacity (CEC) as a measure of high-density lipoprotein functionality is independently and inversely associated with increased risk of cardiovascular events and mortality, and advanced plaque morphology. Adipokines, adipose tissue-derived factors, can influence systemic lipoprotein metabolism, and participate in the regulation of vascular function and inflammation. We aimed to investigate the association between CEC and circulating adipokine levels (anti-inflammatory adiponectin, and pro-inflammatory chemerin and resistin) in subjects with severe carotid atherosclerotic disease and evaluate its impact on post-surgical outcomes. METHODS AND RESULTS This is a cross-sectional study with a 5-year follow-up component. Consecutive patients with severe carotid atherosclerosis scheduled for a carotid endarterectomy were recruited from hospital-based centres in Montreal, Canada (n = 285). Fasting blood samples were collected pre-operatively and used to measure plasma total and high-molecular weight (HMW) adiponectin, chemerin, and resistin, and to perform cholesterol efflux assays in J774 macrophage-like cells. Five-year post-surgery outcomes were obtained through medical chart review. Subjects had a mean age of 70.1 ± 9.4, were 67.0 % male, had various comorbidities (hypercholesterolemia [85.3 %], hypertension [83.5 %], type 2 diabetes [34.5 %], coronary artery disease [38.6 %]), and previously experienced cerebrovascular symptomatology (77.9 %). CEC was independently and positively associated with total and HMW adiponectin levels (ß [95 % confidence interval]; 0.216 [0.134-0.298] and 0.107 [0.037-0.176], respectively) but not with chemerin or resistin. Total adiponectin had the greatest association accounting for 8.3 % of the variance in CEC. Interaction regression models demonstrated a significant interaction between adiponectin and chemerin in increasing CEC. Notably, with each unit increase in CEC there was a 93.9 % decrease in the odds of having an ischemic cerebrovascular event 5 years post-surgery (0.061 [0.007-0.561]). CONCLUSIONS Our findings demonstrated circulating adiponectin to have a strong association with increased CEC in subjects with severe carotid atherosclerosis and high CEC to be associated with more favourable post-surgical outcomes. These findings reflect the importance of adipose tissue health in influencing CEC levels and atherosclerotic cardiovascular disease risk.
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Affiliation(s)
- Karina Gasbarrino
- Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
| | - Anouar Hafiane
- Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
| | - Ioanna Gianopoulos
- Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
| | - Huaien Zheng
- Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada
| | - Christos S Mantzoros
- Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States; Section of Endocrinology, Diabetes and Metabolism, Boston VA Healthcare System, Boston, MA, United States
| | - Stella S Daskalopoulou
- Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, Research Institute of the McGill University Health Centre, McGill University Montreal, Canada; Division of Internal Medicine, Department of Medicine, Faculty of Medicine, McGill University Health Centre, McGill University Montreal, Canada.
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27
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Sanches JM, Zhao LN, Salehi A, Wollheim CB, Kaldis P. Pathophysiology of type 2 diabetes and the impact of altered metabolic interorgan crosstalk. FEBS J 2023; 290:620-648. [PMID: 34847289 DOI: 10.1111/febs.16306] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 10/14/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023]
Abstract
Diabetes is a complex and multifactorial disease that affects millions of people worldwide, reducing the quality of life significantly, and results in grave consequences for our health care system. In type 2 diabetes (T2D), the lack of β-cell compensatory mechanisms overcoming peripherally developed insulin resistance is a paramount factor leading to disturbed blood glucose levels and lipid metabolism. Impaired β-cell functions and insulin resistance have been studied extensively resulting in a good understanding of these pathways but much less is known about interorgan crosstalk, which we define as signaling between tissues by secreted factors. Besides hormones and organokines, dysregulated blood glucose and long-lasting hyperglycemia in T2D is associated with changes in metabolism with metabolites from different tissues contributing to the development of this disease. Recent data suggest that metabolites, such as lipids including free fatty acids and amino acids, play important roles in the interorgan crosstalk during the development of T2D. In general, metabolic remodeling affects physiological homeostasis and impacts the development of T2D. Hence, we highlight the importance of metabolic interorgan crosstalk in this review to gain enhanced knowledge of the pathophysiology of T2D, which may lead to new therapeutic approaches to treat this disease.
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Affiliation(s)
| | - Li Na Zhao
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Albert Salehi
- Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Claes B Wollheim
- Department of Clinical Sciences, Lund University, Malmö, Sweden.,Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland
| | - Philipp Kaldis
- Department of Clinical Sciences, Lund University, Malmö, Sweden
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Johnston EK, Abbott RD. Adipose Tissue Paracrine-, Autocrine-, and Matrix-Dependent Signaling during the Development and Progression of Obesity. Cells 2023; 12:407. [PMID: 36766750 PMCID: PMC9913478 DOI: 10.3390/cells12030407] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/19/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
Obesity is an ever-increasing phenomenon, with 42% of Americans being considered obese (BMI ≥ 30) and 9.2% being considered morbidly obese (BMI ≥ 40) as of 2016. With obesity being characterized by an abundance of adipose tissue expansion, abnormal tissue remodeling is a typical consequence. Importantly, this pathological tissue expansion is associated with many alterations in the cellular populations and phenotypes within the tissue, lending to cellular, paracrine, mechanical, and metabolic alterations that have local and systemic effects, including diabetes and cardiovascular disease. In particular, vascular dynamics shift during the progression of obesity, providing signaling cues that drive metabolic dysfunction. In this review, paracrine-, autocrine-, and matrix-dependent signaling between adipocytes and endothelial cells is discussed in the context of the development and progression of obesity and its consequential diseases, including adipose fibrosis, diabetes, and cardiovascular disease.
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Affiliation(s)
| | - Rosalyn D. Abbott
- Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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Poniedziałek-Czajkowska E, Mierzyński R, Leszczyńska-Gorzelak B. Preeclampsia and Obesity-The Preventive Role of Exercise. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1267. [PMID: 36674022 PMCID: PMC9859423 DOI: 10.3390/ijerph20021267] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/05/2023] [Accepted: 01/08/2023] [Indexed: 06/10/2023]
Abstract
Obesity is now recognized as a worldwide epidemic. An inadequate diet and reduced physical activity are acknowledged as the leading causes of excess body weight. Despite growing evidence that obesity is a risk factor for unsuccessful pregnancies, almost half of all women who become pregnant today are overweight or obese. Common complications of pregnancy in this group of women are preeclampsia and gestational hypertension. These conditions are also observed more frequently in women with excessive weight gain during pregnancy. Preeclampsia is one of the most serious pregnancy complications with an unpredictable course, which in its most severe forms, threatens the life and health of the mother and her baby. The early identification of the risk factors for preeclampsia development, including obesity, allows for the implementation of prophylaxis and a reduction in maternal and fetal complications risk. Additionally, preeclampsia and obesity are the recognized risk factors for developing cardiovascular disease in later life, so prophylaxis and treating obesity are paramount for their prevention. Thus, a proper diet and physical activity might play an essential role in the prophylaxis of preeclampsia in this group of women. Limiting weight gain during pregnancy and modifying the metabolic risk factors with regular physical exercise creates favorable metabolic conditions for pregnancy development and benefits the elements of the pathogenetic sequence for preeclampsia development. In addition, it is inexpensive, readily available and, in the absence of contraindications to its performance, safe for the mother and fetus. However, for this form of prevention to be effective, it should be applied early in pregnancy and, for overweight and obese women, proposed as an essential part of planning pregnancy. This paper aims to present the mechanisms of the development of hypertension in pregnancy in obese women and the importance of exercise in its prevention.
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Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System. Int J Mol Sci 2022; 23:ijms232214296. [PMID: 36430774 PMCID: PMC9695168 DOI: 10.3390/ijms232214296] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Revised: 11/15/2022] [Accepted: 11/16/2022] [Indexed: 11/19/2022] Open
Abstract
Obesity with its associated complications represents a social, economic and health problem of utmost importance worldwide. Specifically, obese patients carry a significantly higher risk of developing cardiovascular disease compared to nonobese individuals. Multiple molecular mechanisms contribute to the impaired biological activity of the distinct adipose tissue depots in obesity, including secretion of proinflammatory mediators and reactive oxygen species, ultimately leading to an unfavorable impact on the cardiovascular system. This review summarizes data relating to the contribution of the main adipose tissue depots, including both remote (i.e., intra-abdominal, hepatic, skeletal, pancreatic, renal, and mesenteric adipose fat), and cardiac (i.e., the epicardial fat) adipose locations, on the cardiovascular system. Finally, we discuss both pharmacological and non-pharmacological strategies aimed at reducing cardiovascular risk through acting on adipose tissues, with particular attention to the epicardial fat.
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Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response. Pharmacol Ther 2022; 238:108274. [DOI: 10.1016/j.pharmthera.2022.108274] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/11/2022] [Accepted: 08/23/2022] [Indexed: 11/20/2022]
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Pamuk F, Kantarci A. Inflammation as a link between periodontal disease and obesity. Periodontol 2000 2022; 90:186-196. [PMID: 35916870 DOI: 10.1111/prd.12457] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Nutrition plays a critical role in the homeostatic balance, maintenance of health, and longevity. There is a close link between inflammatory diseases and nutritional health. Obesity is a severe pathological process with grave implications on several organ systems and disease processes, including type 2 diabetes, cardiovascular disease, osteoarthritis, and rheumatoid arthritis. The impact of obesity on periodontal inflammation has not been fully understood; the association between nutritional balance and periodontal inflammation is much less explored. This review is focused on the potential mechanistic links between periodontal diseases and obesity and common inflammatory activity pathways that can be pharmacologically targeted.
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Affiliation(s)
- Ferda Pamuk
- Forsyth Institute, Cambridge, Massachusetts, USA.,Department of Oral Health Sciences, University of Leuven (KU Leuven), Leuven, Belgium
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Roy N, Haddad D, Yang W, Rosas SE. Adipokines and coronary artery calcification in incident dialysis participants. Endocrine 2022; 77:272-280. [PMID: 35751773 DOI: 10.1007/s12020-022-03111-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 06/10/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE Adipokines have been associated with increased risk of cardiovascular disease. Our aim was to determine if adipokine levels are associated with coronary artery calcification (CAC) as well as all-cause mortality in incident dialysis patients. METHODS In patients new to dialysis, we prospectively investigated the association of adiponectin, leptin and resistin with coronary artery calcification measured by ECG-gated computer tomography. Participants were recruited a median of two months after starting dialysis. RESULTS The mean age was 50.0 (12.6) years and 31.1% were women. About 42% percent had BMI > 30. Higher adiponectin levels were inversely associated with CAC progression as change in Agatston score [-155.1 (-267.9, -42.2), p = 0.008] or change in CAC volumes between scans [-2.8 (-4.9, -0.6), p = 0.01]. Higher leptin levels were associated with CAC progression [110.4 (34.3-186.6), p = 0.005]. Decreased leptin [HR 0.5 (0.3-0.9), p = 0.05] was associated with all-cause mortality in adjusted models. There was no significant association between all-cause mortality and adiponectin [1.4 (0.6-3.4), p = 0.4] or resistin [HR 1.7 (0.5-5.0), p = 0.4]. CONCLUSION High adiponectin protects against CAC progression, but is not associated with increased all-cause mortality. Higher leptin, as well as higher leptin to adiponectin ratio, is associated with CAC progression. Lower leptin levels were associated with all-cause mortality. The association of adipokines and cardiovascular disease in individuals on dialysis is complex and requires further study.
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Affiliation(s)
- Neil Roy
- Kidney and Hypertension Unit, Joslin Diabetes Center, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Danny Haddad
- RWJ Barnabas -Jersey City Medical Center, Jersey City, NJ, USA
| | - Wei Yang
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Sylvia E Rosas
- Kidney and Hypertension Unit, Joslin Diabetes Center, Boston, MA, USA.
- Harvard Medical School, Boston, MA, USA.
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Abstract
Obesity has reached epidemic proportions and is a major contributor to insulin resistance (IR) and type 2 diabetes (T2D). Importantly, IR and T2D substantially increase the risk of cardiovascular (CV) disease. Although there are successful approaches to maintain glycemic control, there continue to be increased CV morbidity and mortality associated with metabolic disease. Therefore, there is an urgent need to understand the cellular and molecular processes that underlie cardiometabolic changes that occur during obesity so that optimal medical therapies can be designed to attenuate or prevent the sequelae of this disease. The vascular endothelium is in constant contact with the circulating milieu; thus, it is not surprising that obesity-driven elevations in lipids, glucose, and proinflammatory mediators induce endothelial dysfunction, vascular inflammation, and vascular remodeling in all segments of the vasculature. As cardiometabolic disease progresses, so do pathological changes in the entire vascular network, which can feed forward to exacerbate disease progression. Recent cellular and molecular data have implicated the vasculature as an initiating and instigating factor in the development of several cardiometabolic diseases. This Review discusses these findings in the context of atherosclerosis, IR and T2D, and heart failure with preserved ejection fraction. In addition, novel strategies to therapeutically target the vasculature to lessen cardiometabolic disease burden are introduced.
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Conte M, Petraglia L, Poggio P, Valerio V, Cabaro S, Campana P, Comentale G, Attena E, Russo V, Pilato E, Formisano P, Leosco D, Parisi V. Inflammation and Cardiovascular Diseases in the Elderly: The Role of Epicardial Adipose Tissue. Front Med (Lausanne) 2022; 9:844266. [PMID: 35242789 PMCID: PMC8887867 DOI: 10.3389/fmed.2022.844266] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 01/13/2022] [Indexed: 01/08/2023] Open
Abstract
Human aging is a complex phenomenon characterized by a wide spectrum of biological changes which impact on behavioral and social aspects. Age-related changes are accompanied by a decline in biological function and increased vulnerability leading to frailty, thereby advanced age is identified among the major risk factors of the main chronic human diseases. Aging is characterized by a state of chronic low-grade inflammation, also referred as inflammaging. It recognizes a multifactorial pathogenesis with a prominent role of the innate immune system activation, resulting in tissue degeneration and contributing to adverse outcomes. It is widely recognized that inflammation plays a central role in the development and progression of numerous chronic and cardiovascular diseases. In particular, low-grade inflammation, through an increased risk of atherosclerosis and insulin resistance, promote cardiovascular diseases in the elderly. Low-grade inflammation is also promoted by visceral adiposity, whose accumulation is paralleled by an increased inflammatory status. Aging is associated to increase in epicardial adipose tissue (EAT), the visceral fat depot of the heart. Structural and functional changes in EAT have been shown to be associated with several heart diseases, including coronary artery disease, aortic stenosis, atrial fibrillation, and heart failure. EAT increase is associated with a greater production and secretion of pro-inflammatory mediators and neuro-hormones, so that thickened EAT can pathologically influence, in a paracrine and vasocrine manner, the structure and function of the heart and is associated to a worse cardiovascular outcome. In this review, we will discuss the evidence underlying the interplay between inflammaging, EAT accumulation and cardiovascular diseases. We will examine and discuss the importance of EAT quantification, its characteristics and changes with age and its clinical implication.
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Affiliation(s)
- Maddalena Conte
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
- Casa di Cura San Michele, Maddaloni, Italy
| | - Laura Petraglia
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | | | | | - Serena Cabaro
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Pasquale Campana
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Giuseppe Comentale
- Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy
| | - Emilio Attena
- Department of Cardiology, Monaldi Hospital, Naples, Italy
| | - Vincenzo Russo
- Department of Medical Translational Sciences, Monaldi Hospital, University of Campania Luigi Vanvitelli, Campania, Italy
| | - Emanuele Pilato
- Department of Advanced Biomedical Science, University of Naples Federico II, Naples, Italy
| | - Pietro Formisano
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Dario Leosco
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
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Mojtahedi S, Hooshmand-Moghadam B, Rosenkranz S, Shourideh Z, Amirshaghaghi F, Shabkhiz F. Improvement of inflammatory status following saffron (Crocus sativus L.) and resistance training in elderly hypertensive men: A randomized controlled trial. Exp Gerontol 2022; 162:111756. [DOI: 10.1016/j.exger.2022.111756] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 02/20/2022] [Accepted: 02/24/2022] [Indexed: 11/04/2022]
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The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27020334. [PMID: 35056647 PMCID: PMC8781412 DOI: 10.3390/molecules27020334] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/30/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
Abstract
Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.
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Sweeney T, Ogunmoroti O, Ndumele CE, Zhao D, Varma B, Allison MA, Budoff MJ, Fashanu OE, Sharma A, Bertoni AG, Michos ED. Associations of adipokine levels with the prevalence and extent of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2021; 338:15-22. [PMID: 34785427 PMCID: PMC8665862 DOI: 10.1016/j.atherosclerosis.2021.11.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/16/2021] [Accepted: 11/02/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Extra-coronary calcification (ECC) is a marker of atherosclerosis and independently associated with cardiovascular disease (CVD). Adipokines may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well-established. We examined the associations of leptin, resistin and adiponectin with ECC in a diverse community-based cohort. METHODS We performed a cross-sectional analysis of 1897 adults without clinical CVD in the MESA cohort. Serum adipokine levels and non-contrast cardiac CT scans were obtained at Exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin [per 1 SD ln(adipokine] with ECC prevalence (score >0) and extent [ln(score+1)]. RESULTS The mean age of participants was 65 ± 10 years; 49% women. After adjusting for demographic factors, adiponectin was inversely associated with AVC prevalence and extent; leptin positively associated with MAC prevalence and extent; and resistin positively associated with ATAC prevalence and extent and DTAC extent. After adjustment for BMI and other CVD risk factors, adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC after full adjustment. CONCLUSIONS We identified significant associations between select adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.
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Affiliation(s)
- Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Oluseye Ogunmoroti
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Chiadi E Ndumele
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Di Zhao
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bhavya Varma
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthew A Allison
- Department of Family Medicine, University of California San Diego, San Diego, CA, USA
| | | | | | - Apurva Sharma
- Icahn School of Medicine, Mount Sinai Hospital, New York City, NY, USA
| | - Alain G Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Lee KO, Lee KY, Lee CY, Kim JH, Kang J, Lee HY, Na SJ, Oh SH, Heo JH. High Serum Levels of Resistin is Associated With Acute Cerebral Infarction. Neurologist 2021; 27:41-45. [PMID: 34842580 PMCID: PMC8900991 DOI: 10.1097/nrl.0000000000000362] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND The inflammatory process is involved in the pathogenesis of atherosclerosis and brain tissue injury following cerebral ischemia. Human resistin is a member of small cysteine-rich secreted proteins and has been implicated in inflammatory responses. This study investigated the association of serum resistin level with acute cerebral infarction (ACI). We also investigated its association with the short-term functional outcome. METHODS This study included 106 patients with ACI and 106 age-matched and sex-matched healthy control subjects. Serum resistin level was assessed by using enzyme-linked immunosorbent sandwich assay. The association of serum resistin levels with ACI was analyzed by logistic regression analysis. RESULTS The serum resistin level was significantly higher in patients with ACI than the control group [median (interquartile range), 35.7 ng/mL (13.0 to 70.5) ng/mL vs. 10.5 ng/ml (15.4 to 16.6), P<0.001]. Logistic regression analysis showed that serum resistin level was associated with an ACI (odds ratio=1.055, 95% confidence interval: 1.035-1.074, P<0.001). Among stroke subtypes, the serum resistin level was higher in the patients with large artery atherosclerosis than those with other subtypes (P=0.013). High resistin levels were also significantly associated with unfavorable functional outcome at discharge (odds ratio=1.043, 95% confidence interval: 1.024-1.063, P<0.001). CONCLUSIONS This study suggests the potential association of resistin with stroke and cerebral atherosclerosis. Increased serum resistin levels were also associated with early unfavorable neurological outcome.
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Affiliation(s)
- Kee Ook Lee
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam
- Myunggok Medical Research Institute
| | - Kyung-Yul Lee
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
| | | | - Ji Hoon Kim
- Department of Neurology, Daejeon Sun Hospital, Daejeon
| | | | | | - Sang-Jun Na
- Neurology, Konyang University College of Medicine
| | - Seung-Hun Oh
- Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam
| | - Ji Hoe Heo
- Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
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Álvarez-Vásquez JL, Bravo-Guapisaca MI, Gavidia-Pazmiño JF, Intriago-Morales RV. Adipokines in dental pulp: physiological, pathological, and potential therapeutic roles. J Oral Biosci 2021; 64:59-70. [PMID: 34808362 DOI: 10.1016/j.job.2021.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/12/2021] [Accepted: 11/15/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hundreds of adipokines have been identified, and their extensive range of endocrine functions-regulating distant organs such as oral tissues-and local autocrine/paracrine roles have been studied. In dentistry, however, adipokines are poorly known proteins in the dental pulp; few of them have been studied despite their large number. This study reviews recent advances in the investigation of dental-pulp adipokines, with an emphasis on their roles in inflammatory processes and their potential therapeutic applications. HIGHLIGHTS The most recently identified adipokines in dental pulp include leptin, adiponectin, resistin, ghrelin, oncostatin, chemerin, and visfatin. They have numerous physiological and pathological functions in the pulp tissue: they are closely related to pulp inflammatory mechanisms and actively participate in cell differentiation, mineralization, angiogenesis, and immune-system modulation. CONCLUSION Adipokines have potential clinical applications in regenerative endodontics and as biomarkers or targets for the pharmacological management of inflammatory and degenerative processes in dental pulp. A promising direction for the development of new therapies may be the use of agonists/antagonists to modulate the expression of the most studied adipokines.
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Metwalli O, Hashem E, Ajabnoor MA, Alama N, Banjar ZM. Study of Some Inflammatory Mediators in the Serum of Patients With Atherosclerosis and Acute Myocardial Infarction. Cureus 2021; 13:e18450. [PMID: 34745775 PMCID: PMC8561326 DOI: 10.7759/cureus.18450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2021] [Indexed: 11/21/2022] Open
Abstract
Background and aim of the study The aim of this study is to evaluate the changes in the inflammatory mediator's serum amyloid A (SAA), adiponectin, and resistin in the serum of patients with stable angina and acute myocardial infarction. Subjects and methods The study was done on 60 subjects divided into three groups: 20 healthy normal individuals as a control group, 20 patients with stable angina (atherosclerotic plaque), and 20 patients with myocardial infarction. Fasting blood samples were withdrawn from all subjects and serum was prepared. SAA, resistin, and adiponectin levels were quantitatively measured by enzyme-linked immunosorbent assay (ELISA). Results The SAA level was significantly higher in both stable angina and the acute myocardial infarction group than the control group (2.7179 ± 0.44501 mg/L) and the serum resistin level was significantly higher (p-value = 0.0) in the stable angina (8.368 ± 1.633 ng/ml) and the acute myocardial infarction (13.606 ± 2.067 ng/ml) groups (p-value= 0.0) than the control group. (2.4272±1.25210 ng/ml). Moreover, resistin levels in stable angina when compared to the AMI showed a significant difference between them (p-value = 0.0) while adiponectin was significantly lower in the acute myocardial infarction group. (6.641±2.6011 µg/mL, p-value = 0.019) than its level in the control group (11.873±1.798 µg/mL). While the adiponectin level showed no significant differences between stable angina in comparison to the AMI. Conclusion SAA can be used as a confirmatory marker for stable angina and a diagnostic tool for AMI patients. Both SAA and resistin may participate in the atherosclerosis process as an effectors molecule of inflammatory reactions. For adiponectin, we concluded that it has the antiatherogenic property and its levels were lower in both the stable angina and acute myocardial infarction groups.
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Affiliation(s)
- Ohoud Metwalli
- Pathology, Department of Laboratory, King Abdulaziz University Hospital, Jeddah, SAU
| | - Enayat Hashem
- Clinical Biochemistry, King Abdulaziz University Faculty of Medicine, Jeddah, SAU
| | | | - Nabil Alama
- Cardiology, Department of Medicine, King Abdulaziz University Hospital, Jeddah, SAU
| | - Zainy M Banjar
- Clinical Biochemistry, King Abdulaziz University Faculty of Medicine, Jeddah, SAU
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Hinson HE, Li P, Myers L, Agarwal C, Pollock J, McWeeney S. Incorporating Immunoproteins in the Development of Classification Models of Progression of Intracranial Hemorrhage After Traumatic Brain Injury. J Head Trauma Rehabil 2021; 36:E322-E328. [PMID: 33656476 PMCID: PMC8380269 DOI: 10.1097/htr.0000000000000654] [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] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To define clinical, radiographic, and blood-based biomarker features to be incorporated into a classification model of progression of intracranial hemorrhage (PICH), and to provide a pilot assessment of those models. METHODS Patients with hemorrhage on admission head computed tomography were identified from a prospectively enrolled cohort of subjects with traumatic brain injury. Initial and follow-up images were interpreted both by 2 independent readers, and disagreements adjudicated. Admission plasma samples were analyzed and principal components (PCs) composed of the immune proteins (IPs) significantly associated with the outcome of interest were selected for further evaluation. A series of logistic regression models were constructed based on (1) clinical variables (CV) and (2) clinical variables + immune proteins (CV+IP). Error rates of these models for correct classification of PICH were estimated; significance was set at P < .05. RESULTS We identified 106 patients, 36% had PICH. Dichotomized admission Glasgow Coma Scale (P = .004), Marshall score (P = .004), and 3 PCs were significantly associated with PICH. For the CV only model, sensitivity was 1.0 and specificity was 0.29 (95% CI, 0.07-0.67). The CV+IP model performed significantly better, with a sensitivity of 0.93 (95% CI, 0.64-0.99) and a specificity of 1.0 (P = .008). Adjustments to refine the definition of PICH and better define radiographic predictors of PICH did not significantly improve the models' performance. CONCLUSIONS In this pilot investigation, we observed that composites of IPs may improve PICH classification models when combined with CVs. However, overall model performance must be further optimized; results will inform feature inclusion included in follow-up models.
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Affiliation(s)
- H E Hinson
- Departments of Neurology (Drs Hinson and Agarwal and Mr Myers) and Radiology (Drs Li and Pollock), and Division of Bioinformatics & Computational Biology, Department of Medical Informatics and Clinical Epidemiology (Dr McWeeney), Oregon Health & Sciences University, Portland
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Serum resistin is predictive marker of development of new digital ulcers in systemic sclerosis. Clin Exp Med 2021; 22:421-426. [PMID: 34462844 PMCID: PMC9338111 DOI: 10.1007/s10238-021-00756-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 08/19/2021] [Indexed: 11/04/2022]
Abstract
Systemic sclerosis (SSc) is autoimmune disease characterized by endothelial dysfunction and microvascular damage. Resistin has been implied in microvascular dysfunction. Objective of this study is to evaluate the association between baseline resistin and development of new digital ulcers (DUs) in SSc patients. At baseline, serum resistin has been assessed in 70 female SSc patients and 26 healthy controls (HC). In SSc patients, clinical assessment was performed at baseline and after a 52-weeks follow-up. Serum resistin level was increased in SSc patients compared to HC [5.89 ng/ml (2.5 ng/ml–8.1 ng/ml) vs 2.3 ng/ml (0.4 ng/ml–2.4 ng/ml), p = 0.0004)]. Resistin was lower (p = 0.005) in SSc patients with early capillaroscopic pattern than patients with active or late capillaroscopic pattern [2.49 ng/ml (0.89 ng/ml–5.81 ng/ml) vs 7.11 ng/ml (3.48 ng/ml–11.35 ng/ml) and 6.49 ng/ml (3.35 ng/ml–8.87 ng/ml), respectively]. After a 52-weeks follow-up, 34 (48.6%) patients developed new DUs. Median serum resistin was significantly higher in patients with new DUs than in patients without new DUs [6.54 ng/ml (3.35 ng/ml–11.02 ng/ml) vs 4.78 ng/ml (1.06 ng/ml–7.6 ng/ml), p = 0.019]. Kaplan–Meier curves show a significantly reduced free survival from DUs in patients with increased resistin (p = 0.002). In multivariate analysis, resistin is associated with the development of new DUs. Increased serum resistin level is a predictive marker of new DUs in SSc.
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44
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Močnik M, Marčun Varda N. Cardiovascular Risk Factors in Children with Obesity, Preventive Diagnostics and Possible Interventions. Metabolites 2021; 11:551. [PMID: 34436493 PMCID: PMC8398426 DOI: 10.3390/metabo11080551] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 07/30/2021] [Accepted: 08/10/2021] [Indexed: 12/16/2022] Open
Abstract
The increasing burden of obesity plays an essential role in increased cardiovascular morbidity and mortality. The effects of obesity on the cardiovascular system have also been demonstrated in childhood, where prevention is even more important. Obesity is associated with hormonal changes and vascular dysfunction, which eventually lead to hypertension, hyperinsulinemia, chronic kidney disease, dyslipidemia and cardiac dysfunction-all associated with increased cardiovascular risk, leading to potential cardiovascular events in early adulthood. Several preventive strategies are being implemented to reduce the cardiovascular burden in children. This paper presents a comprehensive review of obesity-associated cardiovascular morbidity with the preventive diagnostic workup at our hospital and possible interventions in children.
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Affiliation(s)
- Mirjam Močnik
- Department of Paediatrics, University Medical Centre Maribor, Ljubljanska ulica 5, 2000 Maribor, Slovenia;
| | - Nataša Marčun Varda
- Department of Paediatrics, University Medical Centre Maribor, Ljubljanska ulica 5, 2000 Maribor, Slovenia;
- Medical Faculty, University of Maribor, Taborska 8, 2000 Maribor, Slovenia
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45
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Taouis M, Benomar Y. Is resistin the master link between inflammation and inflammation-related chronic diseases? Mol Cell Endocrinol 2021; 533:111341. [PMID: 34082045 DOI: 10.1016/j.mce.2021.111341] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 01/07/2023]
Abstract
Resistin has been firstly discovered in mice and was identified as an adipose tissue-secreted hormone or adipokine linking obesity and insulin resistance. In humans, resistin has been characterized as a hormone expressed and secreted by Immune cells especially by macrophages, and was linked to many inflammatory responses including inflammation of adipose tissue due to macrophages' infiltration. Human and mouse resistin display sequence and structural similarities and also dissimilarities that could explain their different expression pattern. In mice, strong pieces of evidence clearly associated high resistin plasma levels to obesity and insulin resistance suggesting that resistin could play an important role in the onset and progression of obesity and insulin resistance via resistin-induced inflammation. In humans, the link between resistin and obesity/insulin resistance is still a matter of debate and needs more epidemiological studies. Also, resistin has been linked to other chronic diseases such as cardiovascular diseases and cancers where resistin has been proposed in many studies as a biological marker.
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Affiliation(s)
- Mohammed Taouis
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France.
| | - Yacir Benomar
- Molecular Neuroendocrinology of Food Intake (NMPA), UMR 9197, University of Paris-Saclay, Orsay, France; NMPA, Dept. Development, Evolution and Cell Signaling, Paris-Saclay Institute of Neurosciences (NeuroPSI) CNRS UMR 9197, Orsay, France
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46
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Deb A, Deshmukh B, Ramteke P, Bhati FK, Bhat MK. Resistin: A journey from metabolism to cancer. Transl Oncol 2021; 14:101178. [PMID: 34293684 PMCID: PMC8319804 DOI: 10.1016/j.tranon.2021.101178] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 06/23/2021] [Accepted: 07/09/2021] [Indexed: 12/11/2022] Open
Abstract
Resistin levels have been associated with several pathological disorders such as metabolic disorders, cancers etc. Resistin exists in three isoforms namely RELM-α, β and γ. High resistin level activates inflammatory pathways, promotes metabolic disorders and is associated with carcinogenesis. Increase in the resistin level impairs the therapeutic response by inducing stemness or resistance, in cancer cells. Conventional drugs which alter resistin level could have therapeutic implications in several pathological disorders. Resistin, a small secretory molecule, has been implicated to play an important role in the development of insulin resistance under obese condition. For the past few decades, it has been linked to various cellular and metabolic functions. It has been associated with diseases like metabolic disorders, cardiovascular diseases and cancers. Numerous clinical studies have indicated an increased serum resistin level in pathological disorders which have been reported to increase mortality rate in comparison to low resistin expressing subjects. Various molecular studies suggest resistin plays a pivotal role in proliferation, metastasis, angiogenesis, inflammation as well as in regulating metabolism in cancer cells. Therefore, understanding the role of resistin and elucidating its’ associated molecular mechanism will give a better insight into the management of these disorders. In this article, we summarize the diverse roles of resistin in pathological disorders based on the available literature, clinicopathological data, and a compiled study from various databases. The article mainly provides comprehensive information of its role as a target in different treatment modalities in pre as well as post-clinical studies.
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Affiliation(s)
- Ankita Deb
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Bhavana Deshmukh
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Pranay Ramteke
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Firoz Khan Bhati
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India
| | - Manoj Kumar Bhat
- National Centre for Cell Science, Savitribai Phule Pune University, Ganeshkhind, Pune 411007, India.
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Para I, Albu A, Porojan MD. Adipokines and Arterial Stiffness in Obesity. ACTA ACUST UNITED AC 2021; 57:medicina57070653. [PMID: 34202323 PMCID: PMC8305474 DOI: 10.3390/medicina57070653] [Citation(s) in RCA: 19] [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: 05/30/2021] [Revised: 06/17/2021] [Accepted: 06/21/2021] [Indexed: 12/11/2022]
Abstract
Adipokines are active molecules with pleiotropic effects produced by adipose tissue and involved in obesity-related metabolic and cardiovascular diseases. Arterial stiffness, which is a consequence of arteriosclerosis, has been shown to be an independent predictor of cardiovascular morbidity and mortality. The pathogenesis of arterial stiffness is complex but incompletely understood. Adipokines dysregulation may induce, by various mechanisms, vascular inflammation, endothelial dysfunction, and vascular remodeling, leading to increased arterial stiffness. This article summarizes literature data regarding adipokine-related pathogenetic mechanisms involved in the development of arterial stiffness, particularly in obesity, as well as the results of clinical and epidemiological studies which investigated the relationship between adipokines and arterial stiffness.
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Affiliation(s)
- Ioana Para
- 4th Department of Internal Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania;
| | - Adriana Albu
- 2nd Department of Internal Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania;
- Correspondence:
| | - Mihai D. Porojan
- 2nd Department of Internal Medicine, University of Medicine and Pharmacy “Iuliu Hatieganu”, 400012 Cluj-Napoca, Romania;
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48
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Li Y, Yang Q, Cai D, Guo H, Fang J, Cui H, Gou L, Deng J, Wang Z, Zuo Z. Resistin, a Novel Host Defense Peptide of Innate Immunity. Front Immunol 2021; 12:699807. [PMID: 34220862 PMCID: PMC8253364 DOI: 10.3389/fimmu.2021.699807] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 06/07/2021] [Indexed: 12/24/2022] Open
Abstract
Resistin, a cysteine-rich protein, expressed in adipocytes, was initially proposed as a link between obesity and diabetes in mice. In humans, resistin is considered to be a pro-inflammatory molecule expressed in immune cells, which plays a regulatory role in many chronic inflammatory diseases, metabolic diseases, infectious diseases, and cancers. However, increasing evidence shows that resistin functions as a host defense peptide of innate immunity, in terms of its wide-spectrum anti-microbial activity, modulation of immunity, and limitation of microbial product-induced inflammation. To date, the understanding of resistin participating in host defense mechanism is still limited. The review aims to summarize current knowledge about the biological properties, functions, and related mechanisms of resistin in host defense, which provides new insights into the pleiotropic biological function of resistin and yields promising strategies for developing new antimicrobial therapeutic agents.
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Affiliation(s)
- Yanran Li
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Qiyuan Yang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Dongjie Cai
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Hongrui Guo
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Jing Fang
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Hengmin Cui
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Liping Gou
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Junliang Deng
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zhisheng Wang
- Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, China
| | - Zhicai Zuo
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
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49
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Masi S, Ambrosini S, Mohammed SA, Sciarretta S, Lüscher TF, Paneni F, Costantino S. Epigenetic Remodeling in Obesity-Related Vascular Disease. Antioxid Redox Signal 2021; 34:1165-1199. [PMID: 32808539 DOI: 10.1089/ars.2020.8040] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Significance: The prevalence of obesity and cardiometabolic phenotypes is alarmingly increasing across the globe and is associated with atherosclerotic vascular complications and high mortality. In spite of multifactorial interventions, vascular residual risk remains high in this patient population, suggesting the need for breakthrough therapies. The mechanisms underpinning obesity-related vascular disease remain elusive and represent an intense area of investigation. Recent Advances: Epigenetic modifications-defined as environmentally induced chemical changes of DNA and histones that do not affect DNA sequence-are emerging as a potent modulator of gene transcription in the vasculature and might significantly contribute to the development of obesity-induced endothelial dysfunction. DNA methylation and histone post-translational modifications cooperate to build complex epigenetic signals, altering transcriptional networks that are implicated in redox homeostasis, mitochondrial function, vascular inflammation, and perivascular fat homeostasis in patients with cardiometabolic disturbances. Critical Issues: Deciphering the epigenetic landscape in the vasculature is extremely challenging due to the complexity of epigenetic signals and their function in regulating transcription. An overview of the most important epigenetic pathways is required to identify potential molecular targets to treat or prevent obesity-related endothelial dysfunction and atherosclerotic disease. This would enable the employment of precision medicine approaches in this setting. Future Directions: Current and future research efforts in this field entail a better definition of the vascular epigenome in obese patients as well as the unveiling of novel, cell-specific chromatin-modifying drugs that are able to erase specific epigenetic signals that are responsible for maladaptive transcriptional alterations and vascular dysfunction in obese patients. Antioxid. Redox Signal. 34, 1165-1199.
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Affiliation(s)
- Stefano Masi
- Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italy
| | - Samuele Ambrosini
- Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland
| | - Shafeeq A Mohammed
- Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland
| | - Sebastiano Sciarretta
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.,Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy
| | - Thomas F Lüscher
- Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland.,Heart Division, Royal Brompton and Harefield Hospital Trust, National Heart & Lung Institute, Imperial College, London, United Kingdom
| | - Francesco Paneni
- Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland.,Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland.,Department of Research and Education, University Hospital Zurich, Zurich, Switzerland
| | - Sarah Costantino
- Center for Molecular Cardiology, University of Zürich, Zurich, Switzerland
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50
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Sundararaman SS, Peters LJF, Jansen Y, Gencer S, Yan Y, Nazir S, Bonnin Marquez A, Kahles F, Lehrke M, Biessen EAL, Jankowski J, Weber C, Döring Y, van der Vorst EPC. Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe -/- mice. Sci Rep 2021; 11:10409. [PMID: 34001955 PMCID: PMC8128899 DOI: 10.1038/s41598-021-89893-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 05/04/2021] [Indexed: 01/02/2023] Open
Abstract
The calcium sensing receptor (CaSR) is a G-protein coupled receptor that especially plays an important role in the sensing of extracellular calcium to maintain its homeostasis. Several in-vitro studies demonstrated that CaSR plays a role in adipose tissue metabolism and inflammation, resulting in systemic inflammation and contributing to atherosclerosis development. The aim of this study was to investigate whether adipocyte CaSR plays a role in adipose tissue inflammation in-vivo and atherosclerosis development. By using a newly established conditional mature adipocyte specific CaSR deficient mouse on a hyperlipidemic and atherosclerosis prone Apoe−/− background it could be shown that CaSR deficiency in adipocytes does neither contribute to initiation nor to progression of atherosclerotic plaques as judged by the unchanged lesion size or composition. Additionally, CaSR deficiency did not influence gonadal visceral adipose tissue (vAT) inflammation in-vivo, although a small decrease in gonadal visceral adipose cholesterol content could be observed. In conclusion, adipocyte CaSR seems not to be involved in vAT inflammation in-vivo and does not influence atherosclerosis development in hyperlipidemic Apoe−/− mice.
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Affiliation(s)
- Sai Sahana Sundararaman
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.,Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Linsey J F Peters
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.,Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands.,Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany
| | - Yvonne Jansen
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany
| | - Selin Gencer
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany
| | - Yi Yan
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.,DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
| | - Sumra Nazir
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.,Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Andrea Bonnin Marquez
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.,Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Florian Kahles
- Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany
| | - Michael Lehrke
- Department of Internal Medicine I-Cardiology, University Hospital Aachen, Aachen, Germany
| | - Erik A L Biessen
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Joachim Jankowski
- Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany.,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Christian Weber
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.,DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.,Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands.,Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Yvonne Döring
- Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany.,DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.,Department of Angiology, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Emiel P C van der Vorst
- Interdisciplinary Center for Clinical Research (IZKF), RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. .,Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, Aachen, Germany. .,Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands. .,Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany. .,DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
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