Division of Cardiology, Department of Systems Medicine, Tor Vergata University, 00133 Rome, Italy.
Department of Cardiology, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Int J Mol Sci. 2022 Apr 21;23(9):4589. 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.
糖尿病（DM）是一种葡萄糖代谢紊乱，其特征是由于胰岛素产生和/或作用不足而导致慢性高血糖。DM 影响超过十分之一的成年人，并且与心血管发病率和死亡率增加相关。心血管疾病（CVD）占糖尿病患者总死亡人数的三分之二，其中冠状动脉疾病（CAD）和缺血性心肌病是主要原因。高血糖对血管内皮细胞的损害导致内皮功能障碍，这是糖尿病血管并发症发病机制的主要启动因素；然而，潜在的病理生理机制仍不完全清楚。本综述讨论了 DM 和 CAD 之间的病理生理联系的最新知识，重点介绍了表观遗传修饰的作用，包括 DNA 甲基化、组蛋白修饰和非编码 RNA 调控。对表观遗传机制的深入了解有助于开发具有表观遗传靶点的新型药理学治疗方法（“epidrugs”），尽管这些方法存在一些挑战。特定的表观遗传生物标志物也可用于预测或检测糖尿病并发症的发生和进展。需要进一步研究糖尿病和 CAD 的表观遗传学，以确定可能的新治疗靶点，并通过预测个体药物反应和最小化不良反应来推进个体化医学。
