The Role of Matrix Metalloproteinases in Diabetes Mellitus

Costas      Tsioufis; Ioannis      Bafakis; Alexandros      Kasiakogias; Christodoulos      Stefanadis

doi:10.2174/1568026611208011159

Abstract

Diabetes mellitus (DM) is a leading risk factor for cardiovascular disease that adversely affects multiple vascular components from early in its course. Current evidence implicates matrix metalloproteinases (MMPs) and their endogenous inhibitors in diverse pathways associated with the development and progression of diabetic microvascular complications. In diabetic nephropathy, altered MMPs expression contributes to extracellular matrix deposition and glomerular hypertrophy that eventually lead to proteinuria and renal insufficiency. In diabetic cardiomyopathy, MMPs participate in the breakdown of collagen and elastin, myocardial remodelling as well as the vulnerability of the coronary plaque. The development of diabetic peripheral arterial disease is mediated by the impaired angiogenesis caused by the activity of MMPs. Experimental data support an integral role of MMPs in cerebral circulation and stroke volume in diabetes. An excess of MMPs may contribute in poor diabetic wound healing. Future research should further clarify the role of MMPs within the pathophysiological substrate of diabetes, as well as potential therapeutic options.

Keywords: Diabetes, metalloproteinase, microvascular, atherosclerosis, cardiovascular disease, multiple vascular components, diabetic microvascular complications, glomerular hypertrophy, diabetic cardiomyopathy, collagen, elastin, coronary plaque, pathophysiological, potential therapeutic