{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:16:26Z","timestamp":1791645386859,"version":"4.3.4"},"reference-count":133,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and\/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments (\u201cepidrugs\u201d) with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.<\/jats:p>","DOI":"10.3390\/ijms23094589","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T05:07:22Z","timestamp":1650604042000},"page":"4589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1878-8871","authenticated-orcid":false,"given":"Francesca Romana","family":"Prandi","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"},{"name":"Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalgisio","family":"Lecis","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Illuminato","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialucia","family":"Milite","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1837-5997","authenticated-orcid":false,"given":"Roberto","family":"Celotto","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stamatios","family":"Lerakis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Departmental Faculty of Medicine, Unicamillus-Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0594-7212","authenticated-orcid":false,"given":"Francesco","family":"Barill\u00e0","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2021","journal-title":"Diab. Res. Clin. Pract."},{"key":"ref_2","unstructured":"Magliano, D.J., Boyko, E.J., Balkau, B., Barengo, N., Barr, E., Basit, A., Bhata, D., Bommer, C., Booth, G., and Cariou, B. (2022, April 15). International Diabetes Federation Diabetes Atlas 10th edition. Available online: https:\/\/www.diabetesatlas.org\/en."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2014). Diagnosis and Classification of Diabetes Mellitus. Diab. Care, 37, S81\u2013S90.","DOI":"10.2337\/dc14-S081"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1001\/jama.1979.03290450033020","article-title":"Diabetes and cardiovascular disease. The Framingham study","volume":"241","author":"Kannel","year":"1979","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1046\/j.1523-1755.2000.07705.x","article-title":"The missing link: A single unifying mechanism for diabetic complications","volume":"58","author":"Nishikawa","year":"2000","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2011). Standards of medical care in diabetes\u20132011. Diabetes Care, 34, S11\u2013S61.","DOI":"10.2337\/dc11-S011"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1056\/NEJMc1415677","article-title":"Glycemic Control and Excess Mortality in Type 1 Diabetes","volume":"372","author":"Tornese","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1056\/NEJMoa1504347","article-title":"Excess Mortality among Persons with Type 2 Diabetes","volume":"373","author":"Tancredi","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4239\/wjd.v12.i4.383","article-title":"Diabetic heart disease: A clinical update","volume":"12","author":"Rajbhandari","year":"2021","journal-title":"World J. Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Prandi, F.R., Evangelista, I., Sergi, D., Palazzuoli, A., and Romeo, F. (2022). Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: Molecular abnormalities and phenotypical variants. Heart Fail. Rev., Epub ahead of print.","DOI":"10.1007\/s10741-021-10200-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.2337\/db08-0079","article-title":"Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3","volume":"57","author":"Bugger","year":"2008","journal-title":"Diabetes"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1080\/15548627.2015.1051295","article-title":"Autophagic adaptations in diabetic cardiomyopathy differ between type 1 and type 2 diabetes","volume":"11","author":"Kanamori","year":"2015","journal-title":"Autophagy"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.2337\/diacare.25.7.1135","article-title":"HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: Prospective data from the Verona Diabetes Complications Study","volume":"25","author":"Bonora","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1056\/NEJM199807233390404","article-title":"Mortality from Coronary Heart Disease in Subjects with Type 2 Diabetes and in Nondiabetic Subjects with and without Prior Myocardial Infarction","volume":"339","author":"Haffner","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.amjcard.2012.07.022","article-title":"Comparison of outcomes in patients with versus without diabetes mellitus after revascularization with everolimus- and sirolimus-eluting stents (from the SORT OUT IV trial)","volume":"110","author":"Jensen","year":"2012","journal-title":"Am. J. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1093\/eurheartj\/ehu383","article-title":"Prognostic role of restenosis in 10 004 patients undergoing routine control angiography after coronary stenting","volume":"36","author":"Cassese","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e015372","DOI":"10.1161\/JAHA.119.015372","article-title":"Long-Term (10-Year) Outcomes of Stenting or Bypass Surgery for Left Main Coronary Artery Disease in Patients With and Without Diabetes Mellitus","volume":"9","author":"Lee","year":"2020","journal-title":"J. Am. Hear Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1093\/eurheartj\/ehs393","article-title":"Severity of coronary atherosclerosis in patients with a first acute coronary event: A diabetes paradox","volume":"34","author":"Niccoli","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Poznyak, A., Grechko, A.V., Poggio, P., Myasoedova, V.A., Alfieri, V., and Orekhov, A.N. (2020). The Diabetes Mellitus Atherosclerosis Connection: The Role of Lipid and Glucose Metabolism and Chronic Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051835"},{"key":"ref_20","first-page":"647","article-title":"George Lyman Duff Memorial Lecture. Atherogenesis in diabetes","volume":"12","author":"Bierman","year":"1992","journal-title":"Arter. Thromb. A J. Vasc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/dmr.5610030206","article-title":"Diabetes and atherosclerosis: An epidemiologic view","volume":"3","author":"Pyorala","year":"1987","journal-title":"Diab. Metab. Rev."},{"key":"ref_22","unstructured":"Virchow, R. (1858). Cellular Pathology, John Churchill."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2337\/db12-0420","article-title":"Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes","volume":"62","author":"Lee","year":"2013","journal-title":"Diabetes"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1160\/THS10-11-0739","article-title":"Inflammation and thrombosis in diabetes","volume":"105","author":"Hess","year":"2011","journal-title":"Thromb. Haemost."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/BF00281114","article-title":"Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease: Chicken, egg, or neither?","volume":"26","author":"Jarrett","year":"1984","journal-title":"Diabetologia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2337\/diab.44.4.369","article-title":"Diabetes and Cardiovascular Disease: The \u201cCommon Soil\u201d Hypothesis","volume":"44","author":"Stern","year":"1995","journal-title":"Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2","DOI":"10.3389\/fendo.2018.00002","article-title":"Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links","volume":"9","author":"Arcidiacono","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"623","DOI":"10.2337\/diabetes.48.3.623","article-title":"Paraoxonase 192 Gln\/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes","volume":"48","author":"Pfohl","year":"1999","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1172\/JCI119134","article-title":"Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes","volume":"99","author":"Garin","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.diabres.2010.07.009","article-title":"Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus","volume":"90","author":"Jones","year":"2010","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.2337\/diacare.27.8.2015","article-title":"The +276 G\/T Single Nucleotide Polymorphism of the Adiponectin Gene Is Associated with Coronary Artery Disease in Type 2 Diabetic Patients","volume":"27","author":"Bacci","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.2337\/db06-0613","article-title":"Common Haplotypes at the Adiponectin Receptor 1 (ADIPOR1) Locus Are Associated with Increased Risk of Coronary Artery Disease in Type 2 Diabetes","volume":"55","author":"Soccio","year":"2006","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12933-016-0329-1","article-title":"Apolipoprotein E gene polymorphism and risk of type 2 diabetes and cardiovascular disease","volume":"15","author":"Raslan","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1016\/j.jacc.2011.08.054","article-title":"Genetic Susceptibility to Coronary Heart Disease in Type 2 Diabetes: 3 Independent Studies","volume":"58","author":"Qi","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ijcard.2016.11.088","article-title":"HMGA1 is a novel candidate gene for myocardial infarction susceptibility","volume":"227","author":"Chiefari","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"843","DOI":"10.2337\/dc19-1902","article-title":"Coronary Artery Disease and Type 2 Diabetes: A Proteomic Study","volume":"43","author":"Ferrannini","year":"2020","journal-title":"Diabetes Care"},{"key":"ref_37","first-page":"918267","article-title":"Endothelial Dysfunction and Diabetes: Effects on Angiogenesis, Vascular Remodeling, and Wound Healing","volume":"2012","author":"Kolluru","year":"2012","journal-title":"Int. J. Vasc. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"393","DOI":"10.3343\/alm.2013.33.6.393","article-title":"HbA1c: A Review of Analytical and Clinical Aspects","volume":"33","author":"Weykamp","year":"2013","journal-title":"Ann. Lab. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2337\/dc13-2116","article-title":"Update on Cardiovascular Outcomes at 30 Years of the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications Study","volume":"37","author":"Lachin","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"960","DOI":"10.2337\/diab.43.8.960","article-title":"NIDDM and its metabolic control predict heart disease in elderly subjects","volume":"43","author":"Kuusisto","year":"1994","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1161\/CIRCULATIONAHA.106.621854","article-title":"Advanced glycation end products: Sparking the development of diabetic vascular injury","volume":"114","author":"Goldin","year":"2006","journal-title":"Circulation"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1097\/00004872-200301000-00002","article-title":"Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stifening of aging and diabetes","volume":"21","author":"Aronson","year":"2003","journal-title":"J. Hypertens"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.vph.2018.08.002","article-title":"Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease","volume":"112","author":"Maguire","year":"2019","journal-title":"Vascul. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.jcjd.2013.06.001","article-title":"Molecular mechanisms linking diabetes to the accelerated development of atherosclerosis","volume":"37","author":"Zeadin","year":"2013","journal-title":"Can. J. Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1177\/193229680900300604","article-title":"Hyperglycemia in Critical Illness: A Review","volume":"3","author":"Brealey","year":"2009","journal-title":"J. Diabetes Sci. Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1056\/NEJM199602083340607","article-title":"Mechanisms of disease: Hypertension and associated metabolic abnormalities. The role of insulin resistance and the sympathoadrenal system","volume":"334","author":"Reaven","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"633","DOI":"10.2337\/diab.45.5.633","article-title":"Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM","volume":"45","author":"Carey","year":"1996","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1126\/science.293.5532.1103","article-title":"Genes, genetics, and epigenetics: A correspondence","volume":"293","author":"Wu","year":"2001","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13223-018-0259-4","article-title":"Histone modifications and their role in epigenetics of atopy and allergic diseases","volume":"14","author":"Khalaila","year":"2018","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1161\/CIRCRESAHA.116.306819","article-title":"Epigenetic Changes in Diabetes and Cardiovascular Risk","volume":"118","author":"Keating","year":"2016","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"160692","DOI":"10.1155\/2014\/160692","article-title":"The Role of Ubiquitination and Sumoylation in Diabetic Nephropathy","volume":"2014","author":"Gao","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12943-021-01373-z","article-title":"Histone citrullination: A new target for tumors","volume":"20","author":"Zhu","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2217\/pgs.11.65","article-title":"Pharmacogenomics of oral antidiabetic medications: Current data and pharmacoepigenomic perspective","volume":"12","author":"Manolopoulos","year":"2011","journal-title":"Pharmacogenomics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"16489","DOI":"10.1096\/fj.202000860RR","article-title":"Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications","volume":"34","author":"Scisciola","year":"2020","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.2337\/db08-1666","article-title":"Hyperglycemia Induces a Dynamic Cooperativity of Histone Methylase and Demethylase Enzymes Associated With Gene-Activating Epigenetic Marks That Coexist on the Lysine Tail","volume":"58","author":"Brasacchio","year":"2009","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.bbrc.2013.07.065","article-title":"High glucose induces activation of NF-\u03baB inflammatory signaling through I\u03baB\u03b1 sumoylation in rat mesangial cells","volume":"438","author":"Huang","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.carpath.2008.09.008","article-title":"The ubiquitin\u2013proteasome system contributes to the inflammatory injury in ischemic diabetic myocardium: The role of glycemic control","volume":"18","author":"Marfella","year":"2009","journal-title":"Cardiovasc. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1161\/CIRCGENETICS.114.000671","article-title":"Adverse epigenetic signatures by histone methyltransferase Set7 contribute to vascular dysfunction in patients with type 2 diabetes mellitus","volume":"8","author":"Paneni","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1101\/gr.116095.110","article-title":"Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells","volume":"21","author":"Pirola","year":"2011","journal-title":"Genome Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18091","DOI":"10.1074\/jbc.M311786200","article-title":"In Vivo Chromatin Remodeling Events Leading to Inflammatory Gene Transcription under Diabetic Conditions","volume":"279","author":"Miao","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1161\/CIRCULATIONAHA.113.002887","article-title":"Ten-Eleven Translocation-2 (TET2) Is a Master Regulator of Smooth Muscle Cell Plasticity","volume":"128","author":"Liu","year":"2013","journal-title":"Circulation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1056\/NEJMe0807625","article-title":"UKPDS and the legacy effect","volume":"359","author":"Chalmers","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.1002\/jcp.30185","article-title":"New insight in molecular mechanisms regulating SIRT6 expression in diabetes: Hyperglycaemia effects on SIRT6 DNA methylation","volume":"236","author":"Scisciola","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"109","DOI":"10.18632\/aging.100011","article-title":"SIRT6 stabilizes DNA-dependent Protein Kinase at chromatin for DNA double-strand break repair","volume":"1","author":"McCord","year":"2009","journal-title":"Aging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1084\/jem.20081188","article-title":"Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia","volume":"205","author":"Brasacchio","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2012.12.018","article-title":"Latent Enhancers Activated by Stimulation in Differentiated Cells","volume":"152","author":"Ostuni","year":"2013","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zhang, E., Guo, Q., Gao, H., Xu, R., Teng, S., and Wu, Y. (2015). Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1\/p300\/p53\/p21 Pathway. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143814"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"615","DOI":"10.2131\/jts.40.615","article-title":"Sirt 1 activator inhibits the AGE-induced apoptosis and p53 acetylation in human vascular endothelial cells","volume":"40","author":"Li","year":"2015","journal-title":"J. Toxicol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.2337\/db12-1648","article-title":"SIRT1, p66Shc, and Set7\/9 in Vascular Hyperglycemic Memory","volume":"62","author":"Paneni","year":"2013","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1161\/CIRCRESAHA.111.243592","article-title":"Repression of P66Shc Expression by SIRT1 Contributes to the Prevention of Hyperglycemia-Induced Endothelial Dysfunction","volume":"109","author":"Zhou","year":"2011","journal-title":"Circ. Res."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Bell, C.G., Finer, S., Lindgren, C.M., Wilson, G.A., Rakyan, V.K., Teschendorff, A.E., Akan, P., Stupka, E., Down, T.A., and Prokopenko, I. (2010). Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014040"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000351707","article-title":"IGF2Methylation Is Associated with Lipid Profile in Obese Children","volume":"79","author":"Deodati","year":"2013","journal-title":"Horm. Res. Paediatr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13148-016-0293-3","article-title":"Augmentation of histone deacetylase 3 (HDAC3) epigenetic signature at the interface of proinflammation and insulin resistance in patients with type 2 diabetes","volume":"8","author":"Sathishkumar","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1210\/me.2013-1293","article-title":"Epigenetic Regulation of Macrophage Polarization by DNA Methyltransferase 3b","volume":"28","author":"Yang","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1038\/mtna.2015.23","article-title":"siRNA Versus miRNA as Therapeutics for Gene Silencing","volume":"4","author":"Lam","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Fernandes, J.C.R., Acu\u00f1a, S.M., Aoki, J.I., Floeter-Winter, L.M., and Muxel, S.M. (2019). Long Non-Coding RNAs in the Regulation of Gene Expression: Physiology and Disease. Noncoding RNA, 5.","DOI":"10.3390\/ncrna5010017"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"117837","DOI":"10.1016\/j.lfs.2020.117837","article-title":"Circular RNAs in the pathogenesis of atherosclerosis","volume":"255","author":"Cao","year":"2020","journal-title":"Life Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12933-016-0390-9","article-title":"Oscillating glucose induces microRNA-185 and impairs an efficient antioxidant response in human endothelial cells","volume":"15","author":"Cattaneo","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1124\/jpet.115.226894","article-title":"Molecular Interplay between microRNA-34a and Sirtuin1 in Hyperglycemia-Mediated Impaired Angiogenesis in Endothelial Cells: Effects of Metformin","volume":"356","author":"Arunachalam","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"12565","DOI":"10.1038\/ncomms12565","article-title":"Vascular microRNA-204 is remotely governed by the microbiome and impairs endothelium-dependent vasorelaxation by downregulating Sirtuin1","volume":"7","author":"Vikram","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.devcel.2008.07.002","article-title":"The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis","volume":"15","author":"Wang","year":"2008","journal-title":"Dev. Cell."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.vph.2016.12.002","article-title":"MicroRNA-126 suppresses inflammation in endothelial cells under hyperglycemic condition by targeting HMGB1","volume":"88","author":"Tang","year":"2017","journal-title":"Vascul. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Meng, S., Cao, J., Zhang, X., Fan, Y., Fang, L., Wang, C., Lv, Z., Fu, D., and Li, Y. (2013). Downregulation of MicroRNA-130a Contributes to Endothelial Progenitor Cell Dysfunction in Diabetic Patients via Its Target Runx3. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068611"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.ymthe.2003.10.003","article-title":"Insulin-like Growth Factor I Plasmid Therapy Promotes in Vivo Angiogenesis","volume":"9","author":"Rabinovsky","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.bbrc.2009.02.013","article-title":"microRNA-221 regulates high glucose-induced endothelial dysfunction","volume":"381","author":"Li","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1007\/s00125-011-2125-5","article-title":"MIR221\/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage","volume":"54","author":"Togliatto","year":"2011","journal-title":"Diabetologia"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1161\/CIRCULATIONAHA.110.952325","article-title":"Deregulation of microRNA-503 Contributes to Diabetes Mellitus\u2013Induced Impairment of Endothelial Function and Reparative Angiogenesis After Limb Ischemia","volume":"123","author":"Caporali","year":"2011","journal-title":"Circulation"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.2337\/db10-0208","article-title":"Enhanced Levels of microRNA-125b in Vascular Smooth Muscle Cells of Diabetic db\/db Mice Lead to Increased Inflammatory Gene Expression by Targeting the Histone Methyltransferase Suv39h1","volume":"59","author":"Villeneuve","year":"2010","journal-title":"Diabetes"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/cvr\/cvr300","article-title":"Role of microRNAs in diabetes and its cardiovascular complications","volume":"93","author":"Shantikumar","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.devcel.2008.07.008","article-title":"miR-126 regulates angiogenic signaling and vascular integrity","volume":"15","author":"Fish","year":"2008","journal-title":"Dev. Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"e12436","DOI":"10.1111\/1755-5922.12436","article-title":"Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus","volume":"36","author":"Tang","year":"2018","journal-title":"Cardiovasc. Ther."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.2337\/db14-0298","article-title":"Regulation of Inflammatory Phenotype in Macrophages by a Diabetes-Induced Long Noncoding RNA","volume":"63","author":"Reddy","year":"2014","journal-title":"Diabetes"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zgheib, C., Hodges, M.M., Hu, J., Liechty, K.W., and Xu, J. (2017). Long non-coding RNA Lethe regulates hyperglycemia-induced reactive oxygen species production in macrophages. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177453"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"36340","DOI":"10.1038\/srep36340","article-title":"lncRNA H19\/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1080\/15476286.2016.1220473","article-title":"The emerging landscape of circular RNA in life processes","volume":"14","author":"Qu","year":"2016","journal-title":"RNA Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1016\/j.biopha.2017.09.064","article-title":"Circular RNA hsa_circ_0003575 regulates oxLDL induced vascular endothelial cells proliferation and angiogenesis","volume":"95","author":"Li","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.bbrc.2017.10.068","article-title":"Circular RNA WDR77 target FGF-2 to regulate vascular smooth muscle cells proliferation and migration by sponging miR-124","volume":"494","author":"Chen","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1177\/1479164117722714","article-title":"Hsa-circRNA11783-2 in peripheral blood is correlated with coronary artery disease and type 2 diabetes mellitus","volume":"14","author":"Li","year":"2017","journal-title":"Diabetes Vasc. Dis. Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1002\/agm2.12135","article-title":"Clinical perspectives and concerns of metformin as an anti-aging drug","volume":"3","author":"Wang","year":"2020","journal-title":"Aging Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1186\/s13148-018-0593-x","article-title":"Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals","volume":"10","author":"Elbere","year":"2018","journal-title":"Clin. Epigenet."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.bbadis.2018.01.018","article-title":"Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated H3K79 methylation: Relevance in age-associated vascular dysfunction","volume":"1864","author":"Karnewar","year":"2018","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1038\/onc.2016.391","article-title":"Metformin alters DNA methylation genome-wide via the H19\/SAHH axis","volume":"36","author":"Zhong","year":"2016","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) with the Special Contribution of the Heart Failure Association (HFA) of the ESC","volume":"42","author":"McDonagh","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4253","DOI":"10.1210\/jc.2019-00706","article-title":"The Effects of Dapagliflozin on Systemic and Renal Vascular Function Display an Epigenetic Signature","volume":"104","author":"Solini","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s11101-018-9575-z","article-title":"Phytochemicals and their effective role in the treatment of diabetes mellitus: A short review","volume":"17","author":"Teoh","year":"2018","journal-title":"Phytochem. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"GEG-S12270","DOI":"10.4137\/GEG.S12270","article-title":"Use of Epigenetic Drugs in Disease: An Overview","volume":"6","author":"Heerboth","year":"2014","journal-title":"Genet. Epigenet."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Proshkina, E., Shaposhnikov, M., and Moskalev, A. (2020). Genome-Protecting Compounds as Potential Geroprotectors. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124484"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ijcard.2016.10.058","article-title":"Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial","volume":"227","author":"Mansur","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_109","first-page":"111","article-title":"Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4)","volume":"60","author":"Spanier","year":"2009","journal-title":"J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1017\/S0007114511000316","article-title":"Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients","volume":"106","author":"Molnar","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_111","first-page":"331","article-title":"Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: A double-blind randomized controlled trial with resveratrol supplementation","volume":"55","author":"Bo","year":"2018","journal-title":"Geol. Rundsch."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.diabet.2018.05.010","article-title":"Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial","volume":"45","author":"Sattarinezhad","year":"2019","journal-title":"Diabetes Metab."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1001\/jamacardio.2017.0538","article-title":"Effect of Resveratrol on Walking Performance in Older People With Peripheral Artery Disease: The RESTORE Randomized Clinical Trial","volume":"2","author":"McDermott","year":"2017","journal-title":"JAMA Cardiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/1074248408329608","article-title":"Currying the heart: Curcumin and cardioprotection","volume":"14","author":"Srivastava","year":"2009","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_115","first-page":"868","article-title":"The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats","volume":"118","author":"Morimoto","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.phymed.2012.09.003","article-title":"Curcumin attenuates lipolysis stimulated by tumor necrosis factor-\u03b1 or isoproterenol in 3T3-L1 adipocytes","volume":"20","author":"Xie","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_117","first-page":"273","article-title":"Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers","volume":"36","author":"Soni","year":"1992","journal-title":"Indian J. Physiol. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.2337\/dc12-0116","article-title":"Curcumin Extract for Prevention of Type 2 Diabetes","volume":"35","author":"Chuengsamarn","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13148-019-0696-z","article-title":"Apabetalone (RVX-208) reduces vascular inflammation in vitro and in CVD patients by a BET-dependent epigenetic mechanism","volume":"11","author":"Tsujikawa","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s40256-017-0250-3","article-title":"Selective BET Protein Inhibition with Apabetalone and Cardiovascular Events: A Pooled Analysis of Trials in Patients with Coronary Artery Disease","volume":"18","author":"Nicholls","year":"2017","journal-title":"Am. J. Cardiovasc. Drugs"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1001\/jama.2020.3308","article-title":"Effect of apabetalone added to standard therapy on major adverse cardiovascular events in patients with recent acute coronary syndrome and type 2 diabetes: A randomized clinical trial","volume":"323","author":"Ray","year":"2020","journal-title":"JAMA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1093\/eurheartj\/ehx165","article-title":"Non-coding RNAs in cardiovascular diseases: Diagnostic and therapeutic perspectives","volume":"39","author":"Poller","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13148-016-0170-0","article-title":"Epigenetic associations in relation to cardiovascular prevention and therapeutics","volume":"8","year":"2016","journal-title":"Clin. Epigenet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/j.1440-1681.2006.04403.x","article-title":"ANTISENSE OLIGONUCLEOTIDES: FROM DESIGN TO THERAPEUTIC APPLICATION","volume":"33","author":"Chan","year":"2006","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1161\/ATVBAHA.113.301732","article-title":"Therapeutic Silencing of MicroRNA-33 Inhibits the Progression of Atherosclerosis in Ldlr\u2212\/\u2212 Mice\u2014Brief Report","volume":"33","author":"Rotllan","year":"2013","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1172\/JCI57275","article-title":"Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis","volume":"121","author":"Rayner","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1007\/s00125-015-3622-8","article-title":"Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL\/6 mice","volume":"58","author":"Zheng","year":"2015","journal-title":"Diabetologia"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1161\/ATVBAHA.115.305597","article-title":"Local MicroRNA Modulation Using a Novel Anti-miR-21\u2013Eluting Stent Effectively Prevents Experimental In-Stent Restenosis","volume":"35","author":"Wang","year":"2015","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.jacl.2016.04.013","article-title":"Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia","volume":"10","author":"Duell","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kuespert, S., Heydn, R., Peters, S., Wirkert, E., Meyer, A.-L., Sieb\u00f6rger, M., Johannesen, S., Aigner, L., Bogdahn, U., and Bruun, T.-H. (2020). Antisense Oligonucleotide in LNA-Gapmer Design Targeting TGFBR2\u2014A Key Single Gene Target for Safe and Effective Inhibition of TGF\u03b2 Signaling. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061952"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1038\/ncomms4065","article-title":"A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation","volume":"5","author":"Duivenvoorden","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00395-010-0123-2","article-title":"MicroRNA signatures in total peripheral blood as novel biomarkers for acute myocardial infarction","volume":"106","author":"Meder","year":"2011","journal-title":"Basic. Res. Cardiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1042\/CS20150121","article-title":"Plasma long non-coding RNA, CoroMarker, a novel biomarker for diagnosis of coronary artery disease","volume":"129","author":"Yang","year":"2015","journal-title":"Clin. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4589\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:58:06Z","timestamp":1760137086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,21]]},"references-count":133,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23094589"],"URL":"https:\/\/doi.org\/10.3390\/ijms23094589","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,21]]}}}