Médecine moléculaire et génétique

MicroRNAs and Endothelial Dysfunction in Relation to Obesity and Type 2 Diabetes

Abstract

Dwi Setyowati Karolina, Maskomani Silambarasan, Arunmozhiarasi Armugam and Kandiah Jeyaseelan

The vascular endothelium constitutes an important barrier for the selective passage of plasma proteins, solutes and fluid from the blood to the underlying interstitium and cells. In addition to that, the endothelium also regulates the production of various autocrine and paracrine factors in order to maintain vascular homeostasis. Hence, normal endothelial function is critical for proper vascular activity including blood vessel development and growth (angiogenesis), leukocyte trafficking, coagulation and fibrinolysis. Endothelial dysfunction results from the imbalance between vasoconstriction and vasodilation that predispose the vasculature to leukocyte adherence, endothelial proliferation as well as thrombosis. Several studies have demonstrated the implication of obesity and diabetes in the progression of endothelial dysfunction which in turn accelerates the manifestation of vascular complications. The coexistence between obesity, diabetes and endothelial dysfunction suggests the involvement of common regulators between the three entities. MicroRNAs are promising candidates of these regulators since they have the ability to control the expression of multiple genes that regulate our cellular processes. In fact, dysregulation of microRNAs is a common feature in various human diseases including obese/diabetes-associated vascular complications. This review describes the direct and indirect mechanisms of obesity and diabetes in relation to the manifestation of endothelial dysfunction. At the same time, it also summarizes the latest insights into the implications of microRNAs in the development of endothelial dysfunction and discusses their potential for the treatment of vascular pathophysiological conditions.