Emerging Roles for MicroRNAs in Diabetic Microvascular Disease: Novel Targets for Therapy

• Published in: Endocrine reviews Vol. 38; no. 2; pp. 145 - 168
• Main Authors: Zhang, Yu, Sun, Xinghui, Icli, Basak, Feinberg, Mark W.
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01.04.2017; Copyright Oxford University Press; Oxford University Press
• Subjects: Cardiovascular disease; Cardiovascular diseases; Complications; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - therapy; Diabetic Angiopathies - metabolism; Diabetic Angiopathies - therapy; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - therapy; Disease resistance; Editor's Choice; Gene expression; Health risks; Homeostasis; Humans; Injury prevention; Insulin; Insulin resistance; MicroRNAs; MicroRNAs - metabolism; MicroRNAs - therapeutic use; Microvasculature; miRNA; Nephropathy; Resistance factors; Restoration; Retinopathy; Reviews; Ribonucleic acid; Risk analysis; Risk factors; RNA; Wound healing
• ISSN: 0163-769X; 1945-7189; 1945-7189
• DOI: 10.1210/er.2016-1122

Abstract 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.