MicroRNAs: A Critical Regulator and a Promising Therapeutic and Diagnostic Molecule for Diabetic Cardiomyopathy

Abstract

The risk of heart failure is 2-5 times higher in diabetic patients as compared to non-diabetic patients with similar comorbidities. Recent reports suggest that nearly half of the diabetic population remains undiagnosed, making diabetic cardiomyopathy (DCM) a clinically relevant entity. In the myocardium, chronic hyperglycemia elicits structural and functional abnormalities characterized by ventricular dilation, diastolic dysfunction, fibrosis, and hypertrophy leading to heart failure. Since diabetes is a multifactorial heterogeneous metabolic disorder which cannot be diagnosed or controlled along with coronary artery disease or hypertension, there is an urgent need to understand the underlying molecular mechanisms that leads to DCM and identify potential therapeutic targets. Small non-coding RNAs, in particular, microRNAs (miRNAs), have emerged as key regulators for several life-threatening diseases, including DCM. Recent studies have reported that miRNAs not only regulate the fundamental mechanisms of DCM such as insulin resistance, MAPK pathway, PI3K-AkT pathway, oxidative stress, also inflammatory signaling, but also possess the potential to be a therapeutic or diagnostic target. This review examines the role of critical miRNAs in the onset and pathogenesis of DCM, which also depicts high potential as therapeutic and diagnostic molecule in preclinical studies. Further, it highlights the completed and on-going clinical trials around the globe for diabetes and miRNAs to provide a outlook about the upcoming miRNA therapeutics.

Keywords: Diabetes mellitus; MicroRNAs; clinical trials; critical miRNAs.; diabetic cardiomyopathy; therapeutics.