{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T12:10:12Z","timestamp":1794485412871,"version":"4.9.1"},"reference-count":168,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T00:00:00Z","timestamp":1615507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Desarrollo Cient\u00edfico de Jalisco (FODECIJAL)","award":["8149-2019"],"award-info":[{"award-number":["8149-2019"]}]},{"name":"Fondo de Desarrollo Cient\u00edfico de Jalisco (FODECIJAL)","award":["7941-2019"],"award-info":[{"award-number":["7941-2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.<\/jats:p>","DOI":"10.3390\/cells10030629","type":"journal-article","created":{"date-parts":[[2021,3,12]],"date-time":"2021-03-12T11:56:55Z","timestamp":1615550215000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":120,"title":["Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge"],"prefix":"10.3390","volume":"10","author":[{"given":"Jorge","family":"Guti\u00e9rrez-Cuevas","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Sandoval-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1322-1684","authenticated-orcid":false,"given":"Alejandra","family":"Meza-Rios","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Campus Guadalajara, Zapopan, School of Medicine and Health Sciences, Jalisco 45201, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-5317","authenticated-orcid":false,"given":"Hugo Christian","family":"Monroy-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-1861","authenticated-orcid":false,"given":"Marina","family":"Galicia-Moreno","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-9391","authenticated-orcid":false,"given":"Jes\u00fas","family":"Garc\u00eda-Ba\u00f1uelos","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Santos","sequence":"additional","affiliation":[{"name":"Tecnologico de Monterrey, Campus Guadalajara, Zapopan, School of Medicine and Health Sciences, Jalisco 45201, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7101-9943","authenticated-orcid":false,"given":"Juan","family":"Armendariz-Borunda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, University of Guadalajara, CUCS, Jalisco 44340, Mexico"},{"name":"Tecnologico de Monterrey, Campus Guadalajara, Zapopan, School of Medicine and Health Sciences, Jalisco 45201, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3389\/fendo.2020.00354","article-title":"Role of Leptin in Cardiovascular Diseases","volume":"11","author":"Poetsch","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lubbers, E.R., Price, M.V., and Mohler, P.J. (2018). Arrhythmogenic Substrates for Atrial Fibrillation in Obesity. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01482"},{"key":"ref_3","first-page":"1","article-title":"Prevalence of Obesity Among Adults and Youth: United States, 2015\u20132016","volume":"288","author":"Hales","year":"2017","journal-title":"NCHS Data Brief"},{"key":"ref_4","unstructured":"(2020, February 25). Organization WH: Obesity and Overweight Web Site. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/cphy.c160014","article-title":"Contribution of Maladaptive Adipose Tissue Expansion to Development of Cardiovascular Disease","volume":"7","author":"Jia","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_6","unstructured":"(2020, February 25). Organization WH: Cardiovascular Diseases (CVDs). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cardiovascular-diseases-(cvds)."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1056\/NEJM199910073411501","article-title":"Body-Mass Index and Mortality in a Prospective Cohort of U.S. Adults","volume":"341","author":"Calle","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1136\/jech.49.3.265","article-title":"Body mass index and cardiovascular mortality at different levels of blood pressure: A prospective study of Norwegian men and women","volume":"49","author":"Selmer","year":"1995","journal-title":"J. Epidemiol. Commun. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.atherosclerosis.2017.06.017","article-title":"Impact of the cardiovascular system-associated adipose tissue on atherosclerotic pathology","volume":"263","author":"Chistiakov","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41569-019-0244-8","article-title":"Counter-regulatory renin-angiotensin system in cardiovascular disease","volume":"17","author":"Riquelme","year":"2020","journal-title":"Nat. Rev. Cardiol"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"H1015","DOI":"10.1152\/ajpheart.00023.2006","article-title":"Cardiac fibroblasts: Friend or foe?","volume":"291","author":"Baudino","year":"2006","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/1050-1738(96)00005-9","article-title":"The cell biology of the cardiac interstitium","volume":"6","author":"Borg","year":"1996","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/101979","article-title":"Regulation of Tissue Fibrosis by the Biomechanical Environment","volume":"2013","author":"Carver","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s10557-016-6694-x","article-title":"Can Adiponectin Help us to Target Diastolic Dysfunction?","volume":"30","author":"Francisco","year":"2016","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tcm.2014.09.005","article-title":"Impact of obesity on cardiac metabolism, fibrosis, and function","volume":"25","author":"Mahajan","year":"2015","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"916","DOI":"10.2741\/4257","article-title":"Cross-talk between heme oxygenase and peroxisome proliferator-activated receptors in the regulation of physio-logical functions","volume":"19","author":"Ndisang","year":"2014","journal-title":"Front. Biosci."},{"key":"ref_17","first-page":"1","article-title":"Peroxisome proliferator-activated receptors and their ligands: Nutritional and clinical implications\u2014A re-view","volume":"13","year":"2014","journal-title":"Nutr. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.biochem.77.061307.091829","article-title":"Fat and beyond: The diverse biology of PPARgamma","volume":"77","author":"Tontonoz","year":"2008","journal-title":"Annu. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/271983","article-title":"Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions","volume":"2015","author":"Lee","year":"2015","journal-title":"PPAR Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1152\/physrev.00017.2007","article-title":"Cardiac Remodeling in Obesity","volume":"88","author":"Abel","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.tcm.2016.07.005","article-title":"Biomarkers in cardiovascular disease: Statistical assessment and section on key novel heart failure biomarkers","volume":"27","author":"Dhingra","year":"2017","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the Microbiota in Immunity and Inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s12020-018-1605-5","article-title":"Microbiota and metabolic diseases","volume":"61","author":"Pascale","year":"2018","journal-title":"Endocrine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1161\/HYPERTENSIONAHA.115.05315","article-title":"Gut Dysbiosis Is Linked to Hypertension","volume":"65","author":"Yang","year":"2015","journal-title":"Hypertension"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.ijcard.2014.06.010","article-title":"DNA methylation inhibition: A novel therapeutic strategy for heart failure","volume":"176","author":"Kao","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/nrcardio.2015.71","article-title":"Epigenetic modifications and noncoding RNAs in cardiac hypertrophy and failure","volume":"12","author":"Greco","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.tcm.2012.12.006","article-title":"HDAC-dependent ventricular remodeling","volume":"23","author":"Xie","year":"2013","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.jcmg.2017.04.001","article-title":"Subclinical Myocardial Impairment in Metabolic Diseases","volume":"10","author":"Kosmala","year":"2017","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e007372","DOI":"10.1161\/CIRCIMAGING.117.007372","article-title":"Impact of Epicardial Adipose Tissue, Left Ventricular Myocardial Fat Content, and Interstitial Fibrosis on Myocardial Contractile Function","volume":"11","author":"Ng","year":"2018","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_30","first-page":"1","article-title":"The Role of Obesity in the Development of Left Ventricular Hypertrophy Among Children and Adolescents","volume":"18","author":"Brady","year":"2015","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1161\/CIRCULATIONAHA.117.032474","article-title":"Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity","volume":"137","author":"Packer","year":"2018","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1530\/JME-18-0242","article-title":"Adipose tissue-derived autotaxin causes car-diomyopathy in obese mice","volume":"63","author":"Xu","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11010-010-0546-y","article-title":"Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart","volume":"344","author":"Ballal","year":"2010","journal-title":"Mol. Cell. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jacc.2017.05.043","article-title":"Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution: Part 3 of a 3-Part Series","volume":"70","author":"Niemann","year":"2017","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/8470394","article-title":"Assessment of Mitochondrial Dysfunction and Monoamine Oxidase Contribution to Oxidative Stress in Human Diabetic Hearts","volume":"2016","author":"Duicu","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jacc.2010.09.040","article-title":"Obesity induces signs of premature cardiac aging in younger patients: The role of mitochondria","volume":"57","author":"Niemann","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"H2181","DOI":"10.1152\/ajpheart.00554.2011","article-title":"Oxidative stress and heart failure","volume":"301","author":"Tsutsui","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1573403X14666180111145207","article-title":"Oxidative Stress and Cardiac Remodeling: An Updated Edge","volume":"14","author":"Guillory","year":"2018","journal-title":"Curr. Cardiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1113\/JP271023","article-title":"Tyrosine kinases as key modulators of smooth muscle function in health and disease","volume":"593","author":"Knock","year":"2015","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"365769","DOI":"10.1155\/2012\/365769","article-title":"The Interplay between ROS and Ras GTPases: Physiological and Pathological Impli-cations","volume":"2012","author":"Ferro","year":"2012","journal-title":"J. Signal. Transduct."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1113\/JP276747","article-title":"Cardiomyopathy in obesity, insulin resistance and diabetes","volume":"598","author":"Nakamura","year":"2019","journal-title":"J. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-Mediated Cellular Signaling","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"104","DOI":"10.2174\/157340210791170994","article-title":"Leptin-Induced Sympathetic Nerve Activation: Signaling Mechanisms and Cardiovascular Consequences in Obesity","volume":"6","author":"Rahmouni","year":"2010","journal-title":"Curr. Hypertens. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1097\/HJH.0000000000000149","article-title":"Leptin induces cardiac fibrosis through galectin-3, mTOR and oxidative stress: Potential role in obesity","volume":"32","author":"Bartolome","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2821","DOI":"10.1007\/s11033-020-05360-3","article-title":"Dysregulation of nuclear factor erythroid 2-related factor 2 signaling and activation of fibrogenic pathways in hearts of high fat diet-fed rats","volume":"47","author":"Elrashidy","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fphar.2019.00382","article-title":"Nrf2 as a Potential Mediator of Cardio-vascular Risk in Metabolic Diseases","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.cell.2008.04.041","article-title":"A Redox-Dependent Pathway for Regulating Class II HDACs and Cardiac Hypertrophy","volume":"133","author":"Ago","year":"2008","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/s41401-020-0410-x","article-title":"Compound LM9, a novel MyD88 inhibitor, efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy","volume":"41","author":"Zheng","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13997","DOI":"10.1038\/ncomms13997","article-title":"Saturated palmitic acid induces myocardial inflammatory injuries through direct binding to TLR4 accessory protein MD2","volume":"8","author":"Wang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1161\/CIRCRESAHA.106.142851","article-title":"Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity","volume":"100","author":"Kim","year":"2007","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.lfs.2013.01.003","article-title":"Type II diabetes promotes a myofibroblast phenotype in cardiac fibroblasts","volume":"92","author":"Fowlkes","year":"2013","journal-title":"Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1017\/S1431927611012256","article-title":"Diabetes-Induced Alterations in the Extracellular Matrix and Their Impact on Myocardial Function","volume":"18","author":"Law","year":"2012","journal-title":"Microsc. Microanal."},{"key":"ref_53","first-page":"e00611","article-title":"Myocyte-Derived Hsp90 Modulates Collagen Upregulation via Biphasic Activation of STAT-3 in Fibroblasts during Cardiac Hypertrophy","volume":"37","author":"Datta","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nature24676","article-title":"IL-11 is a crucial determinant of cardiovascular fibrosis","volume":"552","author":"Schafer","year":"2017","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Frangogiannis, N.G. (2020). Cardiac fibrosis. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvaa324"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1111\/j.1742-4658.2007.05709.x","article-title":"Expression and physi-ological role of CCN4\/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes","volume":"274","author":"Yanagita","year":"2007","journal-title":"FEBS J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00018-013-1349-6","article-title":"The pathogenesis of cardiac fibrosis","volume":"71","author":"Kong","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The Biological Basis for Cardiac Repair After Myocardial Infarction: From Inflammation to Fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-Cuevas, J., Sandoval-Rodr\u00edguez, A., Monroy-Ram\u00edrez, H.C., Mercado, M.V.-D., Santos-Garc\u00eda, A., and Armend\u00e1riz-Borunda, J. (2020). Prolonged-release pirfenidone prevents obesity-induced cardiac steatosis and fibrosis in a mouse NASH model. Cardiovasc. Drugs Ther., 1\u201312.","DOI":"10.1016\/j.aohep.2020.08.020"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"776","DOI":"10.7326\/0003-4819-150-11-200906020-00005","article-title":"Narrative review: The emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension","volume":"150","author":"Sowers","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/j.biocel.2008.02.020","article-title":"Molecular regulation of cardiac hypertrophy","volume":"40","author":"Barry","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2008\/173780","article-title":"PPARs\/RXRs in Cardiovascular Physiology and Disease","volume":"2008","author":"Finck","year":"2008","journal-title":"PPAR Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1161\/CIRCULATIONAHA.107.670588","article-title":"Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease","volume":"115","author":"Finck","year":"2007","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.2337\/diab.46.8.1319","article-title":"Tissue Distribution and Quantification of the Expression of mRNAs of Peroxisome Proliferator-Activated Receptors and Liver X Receptor- in Humans: No Alteration in Adipose Tissue of Obese and NIDDM Patients","volume":"46","author":"Auboeuf","year":"1997","journal-title":"Diabetes"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0960-0760(94)90089-2","article-title":"Human and rat peroxisome proliferator activated receptors (PPARs) demonstrate similar tissue distribution but different responsiveness to PPAR activators","volume":"51","author":"Mukherjee","year":"1994","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4318","DOI":"10.1073\/pnas.94.9.4318","article-title":"Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma","volume":"94","author":"Kliewer","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1210\/mend.11.6.0007","article-title":"Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay","volume":"11","author":"Krey","year":"1997","journal-title":"Mol. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.2337\/diabetes.54.8.2460","article-title":"Therapeutic Roles of Peroxisome Proliferator-Activated Receptor Agonists","volume":"54","author":"Staels","year":"2005","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/SHK.0000000000000051","article-title":"Conditional deletion of cardio-myocyte peroxisome proliferator-activated receptor gamma enhances myocardial ischemia-reperfusion injury in mice","volume":"41","author":"Hobson","year":"2014","journal-title":"Shock"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11897-007-0016-3","article-title":"Is there a cardiomyopathy of obesity?","volume":"4","author":"Owan","year":"2007","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gujar, H., Weisenberger, D.J., and Liang, G. (2019). The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epige-nome. Genes, 10.","DOI":"10.3390\/genes10020172"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5512","DOI":"10.1111\/bph.13029","article-title":"The peroxisome proliferator-activated receptors in cardiovascular diseases: Ex-perimental benefits and clinical challenges","volume":"172","author":"Cheang","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1161\/ATVBAHA.112.300665","article-title":"Fenofibrate Inhibits Endothelin-1 Expression by Peroxisome Proliferator\u2013Activated Receptor \u03b1\u2013Dependent and Independent Mechanisms in Human Endothelial Cells","volume":"33","author":"Glineur","year":"2013","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1002\/hep4.1474","article-title":"Pirfenidone Is an Agonistic Ligand for PPARalpha and Improves NASH by Activation of SIRT1\/LKB1\/pAMPK","volume":"4","author":"Staels","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_75","first-page":"dvy016","article-title":"Environmentally induced epigenetic transgenerational inheritance of disease. Environ","volume":"4","author":"Nilsson","year":"2018","journal-title":"Epigenetics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18046","DOI":"10.1073\/pnas.1003540107","article-title":"Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevity","volume":"107","author":"Beekman","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Masi, S., Ambrosini, S., Mohammed, S.A., Sciarretta, S., Luscher, T.F., Paneni, F., and Costantino, S. (2020). Epigenetic Remodeling in Obesi-ty-Related Vascular Disease. Antioxid. Redox Signal.","DOI":"10.1089\/ars.2020.8040"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gad.276568.115","article-title":"Role of TET enzymes in DNA methylation, development, and cancer","volume":"30","author":"Rasmussen","year":"2016","journal-title":"Genes Dev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1016\/S0140-6736(13)62674-4","article-title":"DNA methylation and body-mass index: A genome-wide analysis","volume":"383","author":"Dick","year":"2014","journal-title":"Lancet"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"937","DOI":"10.2217\/epi.15.45","article-title":"HIF3A association with adiposity: The story begins before birth","volume":"7","author":"Pan","year":"2015","journal-title":"Epigenomics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000368425","article-title":"SH2B1 CpG-SNP is associated with body weight reduction in obese subjects following a dietary restriction program","volume":"66","author":"Mansego","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1097\/CCM.0b013e3181b4a854","article-title":"Tumor necrosis factor-\u03b1 decreases sarcoplasmic reticulum Ca2+-ATPase expressions via the promoter methylation in cardiomyocytes*","volume":"38","author":"Kao","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.bbadis.2018.08.015","article-title":"Vascular smooth muscle cell senescence and age-related diseases: State of the art","volume":"1865","author":"Chi","year":"2019","journal-title":"Biochim. Biophys. Acta BBA Mol. Basis Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/1440-1681.12089","article-title":"Heart failure and angiotensin II modulate atrial Pitx2c promotor methylation","volume":"40","author":"Kao","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"5288","DOI":"10.1038\/ncomms6288","article-title":"Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease","volume":"5","author":"Gilsbach","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3389\/fgene.2013.00219","article-title":"Genetics and epigenetics of arrhythmia and heart failure","volume":"4","author":"Duygu","year":"2013","journal-title":"Front. Genet."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Movassagh, M., Choy, M.K., Goddard, M., Bennett, M.R., Down, T.A., and Foo, R.S. (2010). Differential DNA methylation correlates with differ-ential expression of angiogenic factors in human heart failure. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0008564"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8467","DOI":"10.1128\/MCB.24.19.8467-8476.2004","article-title":"Histone Deacetylases 5 and 9 Govern Responsiveness of the Heart to a Subset of Stress Signals and Play Redundant Roles in Heart Development","volume":"24","author":"Chang","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.yjmcc.2015.03.010","article-title":"Non-sirtuin histone deacetylases in the control of cardiac aging","volume":"83","author":"Ferguson","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nature13596","article-title":"A long noncoding RNA protects the heart from pathological hypertrophy","volume":"514","author":"Han","year":"2014","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1161\/HYPERTENSIONAHA.110.154567","article-title":"HDAC inhibition attenuates inflamma-tory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats","volume":"56","author":"Cardinale","year":"2010","journal-title":"Hypertension"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1161\/ATVBAHA.114.303393","article-title":"Histone Deacetylase 9 Represses Cholesterol Efflux and Alternatively Activated Macrophages in Atherosclerosis Development","volume":"34","author":"Cao","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"H1894","DOI":"10.1152\/ajpheart.01039.2011","article-title":"HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats","volume":"302","author":"Usui","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40168-015-0094-5","article-title":"The vocabulary of microbiome research: A proposal","volume":"3","author":"Marchesi","year":"2015","journal-title":"Microbiome"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41367-020-0017-1","article-title":"Obesity Programs of nutrition ER, Assessment G: From obesity through gut microbiota to cardiovascular diseases: A dangerous journey","volume":"10","author":"Marzullo","year":"2020","journal-title":"Int. J. Obes. Suppl."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.coph.2016.01.002","article-title":"Gut microbiome as a novel cardiovascular therapeutic target","volume":"27","author":"Singh","year":"2016","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4291\/wjgp.v6.i4.110","article-title":"New-found link between microbiota and obesity","volume":"6","author":"Chakraborti","year":"2015","journal-title":"World J. Gastrointest. Pathophysiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2217\/fmb.11.142","article-title":"The relationship between gut microbiota and weight gain in humans","volume":"7","author":"Angelakis","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/S2468-1253(17)30147-4","article-title":"The microbiota-gut-brain axis in obesity","volume":"2","author":"Schellekens","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2174\/0929867326666190326113607","article-title":"Obesity and Body Composition in Man and Woman: Associated Diseases and the New Role of Gut Microbiota","volume":"27","author":"Avolio","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.cca.2020.04.037","article-title":"Butyrate-producing bacteria and the gut-heart axis in atherosclerosis","volume":"507","author":"Chen","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/apm.13038","article-title":"Gut microbiota in atherosclerosis: Focus on trimethylamine N-oxide","volume":"128","author":"Zhu","year":"2020","journal-title":"APMIS"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.diabet.2019.10.003","article-title":"The gut microbiota and diabetic cardiomyopathy in humans","volume":"46","author":"Bastin","year":"2020","journal-title":"Diabetes Metab."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Yang, S., Li, X., Yang, F., Zhao, R., Pan, X., Liang, J., Tian, L., Li, X., Liu, L., and Xing, Y. (2019). Gut Microbiota-Dependent Marker TMAO in Promoting Cardiovascular Disease: Inflammation Mechanism, Clinical Prognostic, and Potential as a Therapeutic Target. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01360"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1136\/heartjnl-2015-308826","article-title":"TrimethylamineN-oxide and prognosis in acute heart failure","volume":"102","author":"Suzuki","year":"2016","journal-title":"Heart"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1111\/bph.14933","article-title":"Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice","volume":"177","author":"Du","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41564-018-0272-x","article-title":"Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model","volume":"3","author":"Kasahara","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Mohebali, N., Ekat, K., Kreikemeyer, B., and Breitr\u00fcck, A. (2020). Barrier Protection and Recovery Effects of Gut Commensal Bacteria on Differentiated Intestinal Epithelial Cells In Vitro. Nutrients, 12.","DOI":"10.3390\/nu12082251"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"517","DOI":"10.2217\/fmb.14.140","article-title":"Is there interaction between gut microbial profile and cardiovascular risk in chronic kidney disease patients?","volume":"10","author":"Barros","year":"2015","journal-title":"Future Microbiol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.clinre.2017.09.006","article-title":"Gut microbiota and hypertension: From pathogenesis to new therapeutic strategies","volume":"42","author":"Kang","year":"2018","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/1751-7915.13524","article-title":"The gut microbiota and its interactions with cardiovascular disease","volume":"13","author":"Xu","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1038\/s41588-018-0224-7","article-title":"Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome","volume":"50","author":"Zhernakova","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/joim.12328","article-title":"Microbio-ta-dependent metabolite trimethylamine-N-oxide is associated with disease severity and survival of patients with chronic heart failure","volume":"277","author":"Troseid","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41598-018-37373-1","article-title":"Administration of N-Acyl-Phosphatidylethanolamine Expressing Bacteria to Low Density Lipoprotein Receptor(-\/-) Mice Improves Indices of Cardiometabolic Disease","volume":"9","author":"Chen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"LeComte, V., Kaakoush, N.O., Maloney, C.A., Raipuria, M., Huinao, K.D., Mitchell, H.M., and Morris, M.J. (2015). Changes in Gut Microbiota in Rats Fed a High Fat Diet Correlate with Obesity-Associated Metabolic Parameters. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126931"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","article-title":"A metagenome-wide association study of gut microbiota in type 2 diabetes","volume":"490","author":"Qin","year":"2012","journal-title":"Nature"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2365","DOI":"10.1073\/pnas.0812600106","article-title":"Human gut microbiota in obesity and after gastric bypass","volume":"106","author":"Zhang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-00900-1","article-title":"The gut microbiome in atherosclerotic cardiovascular disease","volume":"8","author":"Jie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/nrcardio.2015.200","article-title":"Heart failure: Gut flora-pathogenic role in chronic heart failure","volume":"13","author":"Lim","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1253\/circj.CJ-18-0468","article-title":"Gut Microbiome and Plasma Microbiome-Related Metabolites in Patients With Decompensated and Compensated Heart Failure","volume":"83","author":"Hayashi","year":"2018","journal-title":"Circ. J."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"530160","DOI":"10.3389\/fcimb.2020.530160","article-title":"Interactions Between Thera-peutics for Metabolic Disease, Cardiovascular Risk Factors, and Gut Microbiota","volume":"10","author":"Ding","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1536\/ihj.16-414","article-title":"Gut Microbiota and Coronary Artery Disease","volume":"57","author":"Yamashita","year":"2016","journal-title":"Int. Heart J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40168-016-0222-x","article-title":"Gut microbiota dysbiosis contributes to the development of hypertension","volume":"5","author":"Li","year":"2017","journal-title":"Microbiome"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4330\/wjc.v12.i4.110","article-title":"Role of gut microbiota in cardio-vascular diseases","volume":"12","author":"Novakovic","year":"2020","journal-title":"World J. Cardiol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4592","DOI":"10.1073\/pnas.1011383107","article-title":"Human oral, gut, and plaque microbiota in patients with atherosclerosis","volume":"108","author":"Koren","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.tips.2018.02.010","article-title":"Emerging Actors in Diabetic Cardiomyopathy: Heartbreaker Biomarkers or Therapeutic Targets?","volume":"39","author":"Palomer","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_128","first-page":"23","article-title":"Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases","volume":"8","author":"Furuhashi","year":"2014","journal-title":"Clin. Med. Insights Cardiol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1515\/cclm-2017-0120","article-title":"Neutrophil gelatinase-associated lipocalin as a risk marker in cardiovascular disease","volume":"56","author":"Sivalingam","year":"2017","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-019-1857-8","article-title":"FNDC5 attenuates obesity-induced cardiac hypertrophy by inactivating JAK2\/STAT3-associated inflammation and oxidative stress","volume":"17","author":"Geng","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.bbrc.2014.06.023","article-title":"p38alpha mitogen-activated kinase mediates car-diomyocyte apoptosis induced by palmitate","volume":"450","author":"Oh","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.clnu.2016.06.002","article-title":"The high-fat diet induces myocardial fibrosis in the metabolically healthy obese minipigs\u2014The role of ER stress and oxidative stress","volume":"36","author":"Li","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Zhang, H., Meng, J., and Yu, H. (2017). Trimethylamine N-oxide Supplementation Abolishes the Cardioprotective Effects of Voluntary Ex-ercise in Mice Fed a Western Diet. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00944"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"H934","DOI":"10.1152\/ajpheart.00238.2018","article-title":"Characterization of a mouse model of obesity-related fibrotic cardiomy-opathy that recapitulates features of human heart failure with preserved ejection fraction","volume":"315","author":"Alex","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/HYPERTENSIONAHA.115.06032","article-title":"Galectin-3 Participates in Cardiovascular Remodeling Associated With Obesity","volume":"66","author":"Rousseau","year":"2015","journal-title":"Hypertension"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"R1560","DOI":"10.1152\/ajpregu.00392.2009","article-title":"Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation","volume":"298","author":"Axelsen","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1054-8807(03)00109-1","article-title":"Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats","volume":"13","author":"Fredersdorf","year":"2004","journal-title":"Cardiovasc. Pathol."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Nguyen, I.T.N., Brandt, M.M., van de Wouw, J., van Drie, R.W.A., Wesseling, M., Cramer, M.J., de Jager, S.C.A., Merkus, D., Duncker, D.J., and Cheng, C. (2020). Both male and female obese ZSF1 rats develop cardiac dysfunction in obesity-induced heart failure with pre-served ejection fraction. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232399"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.metabol.2017.07.007","article-title":"Dipeptidyl peptidase 4 inhibitor attenuates obesity-induced myocardial fibrosis by inhibiting transforming growth factor-betal and Smad2\/3 pathways in high-fat diet-induced obesity rat model","volume":"76","author":"Hong","year":"2017","journal-title":"Metabolism"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"25881","DOI":"10.3390\/ijms161025881","article-title":"Heat Killed Lactobacillus reuteri GMNL-263 Reduces Fibrosis Effects on the Liver and Heart in High Fat Diet-Hamsters via TGF-beta Suppression","volume":"16","author":"Ting","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.amjhyper.2004.11.035","article-title":"Extracellular Matrix Remodeling in the Heart of the Homocysteinemic Obese Rabbit","volume":"18","author":"Carroll","year":"2005","journal-title":"Am. J. Hypertens."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.hrthm.2012.08.043","article-title":"Obesity results in progressive atrial structural and electrical remodeling: Implications for atrial fibrillation","volume":"10","author":"Abed","year":"2013","journal-title":"Heart Rhythm"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Xia, J., Zhang, Y., Xin, L., Kong, S., Chen, Y., Yang, S., and Li, K. (2015). Global Transcriptomic Profiling of Cardiac Hypertrophy and Fatty Heart Induced by Long-Term High-Energy Diet in Bama Miniature Pigs. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132420"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s00125-015-3767-5","article-title":"Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity","volume":"59","author":"Broussard","year":"2015","journal-title":"Diabetologia"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Zhi, H., Luptak, I., Alreja, G., Shi, J., Guan, J., Metes-Kosik, N., and Joseph, J. (2013). Effects of Direct Renin Inhibition on Myocardial Fibrosis and Cardiac Fibroblast Function. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081612"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4103\/0975-7406.80764","article-title":"Aliskiren: An orally active renin inhibitor","volume":"3","author":"Wal","year":"2011","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1161\/01.CIR.102.12.1388","article-title":"Lisinopril-Mediated Regression of Myocardial Fibrosis in Patients With Hypertensive Heart","volume":"102","author":"Brilla","year":"2000","journal-title":"Dis. Circ."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13395-020-00230-9","article-title":"Angioten-sin-converting-enzyme inhibitor prevents skeletal muscle fibrosis in myocardial infarction mice","volume":"10","author":"Kakutani","year":"2020","journal-title":"Skelet. Muscle"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"16087","DOI":"10.1038\/s41598-018-34216-x","article-title":"Pathological cardiac remodeling occurs early in CKD mice from unilateral urinary obstruction, and is attenuated by Enalapril","volume":"8","author":"Ham","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1161\/01.CIR.97.14.1411","article-title":"Angiotensin-converting enzyme inhibitors","volume":"97","author":"Brown","year":"1998","journal-title":"Circulation"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/cvr\/26.7.671","article-title":"Reactive and reparative myocardial fibrosis in arterial hypertension in the rat","volume":"26","author":"Brilla","year":"1992","journal-title":"Cardiovasc. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1159\/000430310","article-title":"Early Spironolactone Treatment Attenuates Heart Failure Development by Improving Myocardial Function and Reducing Fi-brosis in Spontaneously Hypertensive Rats","volume":"36","author":"Cezar","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Oppedisano, F., Macr\u00ec, R., Gliozzi, M., Musolino, V., Carresi, C., Maiuolo, J., Bosco, F., Nucera, S., Zito, M.C., and Guarnieri, L. (2020). The Anti-Inflammatory and Antioxidant Properties of n-3 PUFAs: Their Role in Cardiovascular Protection. Biomedicines, 8.","DOI":"10.3390\/biomedicines8090306"},{"key":"ref_154","first-page":"1553","article-title":"Effects of alpha lipoic acid and pirfenidone on liver cells antioxidant modulation against oxidative damage","volume":"142","author":"Caligiuri","year":"2014","journal-title":"Rev. Med. Chile"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3389\/fphar.2018.00122","article-title":"Therapeutic Potential of Polyphenols in Cardiac Fibrosis","volume":"9","author":"Zhang","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Lyu, X., Hu, M., Peng, J., Zhang, X., and Sanders, Y.Y. (2019). HDAC inhibitors as antifibrotic drugs in cardiac and pulmonary fibrosis. Ther. Adv. Chronic Dis., 10.","DOI":"10.1177\/2040622319862697"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1755-1536-7-10","article-title":"HDAC class I inhibitor, Mocetinostat, reverses cardiac fibrosis in heart failure and diminishes CD90+ cardiac myofibroblast activation","volume":"7","author":"Zakharova","year":"2014","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1139\/cjpp-2018-0430","article-title":"Novel molecular therapeutic targets in cardiac fibrosis: A brief overview","volume":"97","author":"Wang","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1042\/CS20170064","article-title":"Inhibition of HDAC3 prevents diabetic cardiomyopathy in OVE26 mice via epigenetic regulation of DUSP5-ERK1\/2 pathway","volume":"131","author":"Xu","year":"2017","journal-title":"Clin. Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1755-5922.2010.00243.x","article-title":"Allopurinol Attenuates Oxidative Stress and Cardiac Fibrosis in Angiotensin II-Induced Cardiac Diastolic Dysfunction","volume":"30","author":"Jia","year":"2010","journal-title":"Cardiovasc. Ther."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12872-015-0169-z","article-title":"Resveratrol ameliorates myocardial fibrosis by inhibiting ROS\/ERK\/TGF-beta\/periostin pathway in STZ-induced diabetic mice","volume":"16","author":"Wu","year":"2016","journal-title":"BMC Cardiovasc. Disord."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/aps.2017.92","article-title":"Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes","volume":"39","author":"Guo","year":"2017","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1177\/2047487319870344","article-title":"Oxidative stress and inflammation in the evolution of heart failure: From pathophysiology to therapeutic strategies","volume":"27","author":"Aimo","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.trsl.2019.03.001","article-title":"Cardiac fibrosis: Potential therapeutic targets","volume":"209","author":"Park","year":"2019","journal-title":"Transl. Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0168-8278(02)00272-6","article-title":"Pirfenidone effectively reverses experimental liver fibrosis","volume":"37","author":"Sandoval","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1038\/sj.bjp.0704131","article-title":"Reversal of cardiac and renal fibrosis by pirfenidone and spironolactone in streptozotocin-diabetic rats","volume":"133","author":"Miric","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s10557-019-06876-y","article-title":"Pirfenidone in Heart Failure with Preserved Ejection Fraction\u2014Rationale and Design of the PIROUETTE Trial","volume":"33","author":"Lewis","year":"2019","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Parichatikanond, W., Luangmonkong, T., Mangmool, S., and Kurose, H. (2020). Therapeutic Targets for the Treatment of Cardiac Fibrosis and Cancer: Focusing on TGF-beta Signaling. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.00034"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/629\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:34:39Z","timestamp":1760160879000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/629"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,12]]},"references-count":168,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cells10030629"],"URL":"https:\/\/doi.org\/10.3390\/cells10030629","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,12]]}}}