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

Abstract

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.

Mechanistic Studies and a Retrospective Cohort Study: The Interaction between PPAR Agonists and Immunomodulatory Agents in Multiple Myeloma

“…DNA methylation is a biological process by which methyl groups are added to DNA molecules. DNA methylation in a gene promoter typically represses gene transcription [ 32 ]. In our previous research, we checked the sensitivity to lenalidomide in multiple MM cell lines and found that NCIH929 and RPMI8226 (IC50 of 15.39 μM and 17.55 μM, respectively) were relatively sensitive to lenalidomide while U266, OPM1, OPM2, MM1.R, INA6 were resistant to lenalidomide (IC50 of 58.87 μM, 33.71 μM, 42.78 μM, 34.36 μM, and 38.29 μM) [ 25 ].…”

H19 and TUG1 lncRNAs as Novel Biomarkers for Irritable Bowel Syndrome in Diabetic Patients

“…Diabetes and IBS were found to have altered lncRNA expression [ 35 ]. This study showed that diabetic patients with IBS had considerably lower levels of lncRNA H19 expression than healthy controls and diabetic-only patients.…”

Biomolecular Mechanisms of Cardiorenal Protection with Sodium-Glucose Co-Transporter 2 Inhibitors

“…The efficacy of these drugs in the improvement of cardiac function lies also in their epigenetic effects [ 4 ].…”

“…Hyperglycemic damage on vascular endothelial cells, leading to endothelial dysfunction, represents the main initiating factor in the pathogenesis of diabetic micro- and macrovascular complications, in both T1DM and T2DM patients. In addition, T2DM also causes insulin resistance (IR), which is another determinant for endothelial dysfunction [ 4 ]. IR is usually defined as decreased sensitivity to insulin and it plays an important pathophysiological role in the development of prediabetes and T2DM [ 5 ].…”