Zhang Yu, Sun Xinghui, Icli Basak, Feinberg Mark W
Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Department of Pharmacology and Pharmacy, University of Hong Kong, Pokfulam, Hong Kong SAR, China, and.
Endocr Rev. 2017 Apr 1;38(2):145-168. doi: 10.1210/er.2016-1122.
Chronic, low-grade systemic inflammation and impaired microvascular function are critical hallmarks in the development of insulin resistance. Accordingly, insulin resistance is a major risk factor for type 2 diabetes and cardiovascular disease. Accumulating studies demonstrate that restoration of impaired function of the diabetic macro- and microvasculature may ameliorate a range of cardiovascular disease states and diabetes-associated complications. In this review, we focus on the emerging role of microRNAs (miRNAs), noncoding RNAs that fine-tune target gene expression and signaling pathways, in insulin-responsive tissues and cell types important for maintaining optimal vascular homeostasis and preventing the sequelae of diabetes-induced end organ injury. We highlight current pathophysiological paradigms of miRNAs and their targets involved in regulating the diabetic microvasculature in a range of diabetes-associated complications such as retinopathy, nephropathy, wound healing, and myocardial injury. We provide an update of the potential use of circulating miRNAs diagnostically in type I or type II diabetes. Finally, we discuss emerging delivery platforms for manipulating miRNA expression or function as the next frontier in therapeutic intervention to improve diabetes-associated microvascular dysfunction and its attendant clinical consequences.
慢性低度全身炎症和微血管功能受损是胰岛素抵抗发生发展的关键特征。因此，胰岛素抵抗是2型糖尿病和心血管疾病的主要危险因素。越来越多的研究表明，恢复糖尿病大血管和微血管受损的功能可能改善一系列心血管疾病状态以及糖尿病相关并发症。在本综述中，我们关注微小RNA（miRNA）的新作用，miRNA是一类可微调靶基因表达和信号通路的非编码RNA，在对维持最佳血管稳态和预防糖尿病诱导的终末器官损伤后遗症至关重要的胰岛素反应性组织和细胞类型中发挥作用。我们强调了miRNA及其靶标的当前病理生理模式，这些模式参与调节一系列糖尿病相关并发症（如视网膜病变、肾病、伤口愈合和心肌损伤）中的糖尿病微血管。我们提供了循环miRNA在I型或II型糖尿病诊断中潜在用途的最新信息。最后，我们讨论了新兴的递送平台，这些平台可用于操纵miRNA表达或功能，作为治疗干预的下一个前沿领域，以改善糖尿病相关的微血管功能障碍及其伴随的临床后果。
