Medicina Molecular e Genética

Diabetes-Associated Kidney and Vascular Complications: Mechanisms of Disease Progression and Alternative Therapeutic Options

Abstract

Sara Gallo, Maddalena Gili, Gabriele Togliatto and Maria Felice Brizzi

Vascular complications in diabetes are an emergent health care problem. Accelerated endothelial dysfunction in pathological settings connoted by hyperlipidaemia and hyperglycaemia is a crucial step for the development and the progression of atherosclerosis. Previous data support the central role of Advanced Glycated End-products (AGEs) and oxidation or glycation of Low Dense Lipoproteins (LDLs) in the impaired vascular remodelling associated with diabetes. Hyperglycemia, via NADPH Oxidase (NOX) enzymatic activity, upholds the production of Reactive Oxygen Species (ROS), which in turn mediate tissue damage and long-lasting “metabolic memory”. Nonetheless, in diabetic setting, ROS act as secondary messenger to strictly control stemness of visceral-derived adipose stem cells and to promote transcriptional and post-transcriptional events, also involving small non-coding microRNAs (miRs). In this article we provide an overview on the events elicited by acute and chronic hyperglycemia that account for vascular and kidney diseases. The deleterious effects of LDL and fatty acids on endothelial progenitor cells in condition connoted by hyperglycemia are also discussed. Moreover, as current therapeutic approaches failed to improve endothelial dysfunction/disease progression and consequently long-term outcomes in diabetics with vascular complications, particular attention has been devoted to describe efforts made to identify novel therapeutic options, for the management of one of the most relevant health care problems world wide. Finally, as targeting of epigenetic mechanisms is a future challenge, relevant data supporting their deep involvement in long-lasting “metabolic memory” have been also addressed.