Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers

• Published in: International journal of molecular sciences Vol. 23; no. 9; p. 4589
• Main Authors: Prandi, Francesca Romana, Lecis, Dalgisio, Illuminato, Federica, Milite, Marialucia, Celotto, Roberto, Lerakis, Stamatios, Romeo, Francesco, Barillà, Francesco
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.04.2022; MDPI
• Subjects: Atherosclerosis; Cardiomyopathy; Cardiovascular disease; Cardiovascular diseases; Cell cycle; Cell growth; Coronary artery; Coronary artery disease; Coronary Artery Disease - diagnosis; Coronary Artery Disease - genetics; Coronary vessels; Diabetes; Diabetes mellitus; Diabetes Mellitus - diagnosis; Diabetes Mellitus - genetics; DNA methylation; Drug therapy; Endothelial Cells; epidrugs; Epigenesis, Genetic; Epigenetics; Expenditures; Genotype & phenotype; Glucose metabolism; Heart attacks; Heart diseases; Histones; Humans; Hyperglycemia; Hypertension; Inflammation; Insulin; Insulin resistance; Ischemia; Metabolism; Morbidity; Mortality; Pathogenesis; Polymorphism; Precision medicine; Review; Risk factors; RNA, Untranslated - genetics; Therapeutic targets; Vein & artery diseases; coronary artery disease; epidrugs; hyperglycemia; diabetes mellitus; epigenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23094589

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 ("epidrugs") 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.