Aldose Reductase, Oxidative Stress and Diabetic Cardiovascular Complications

Srinivasan      Vedantham; Radha      Ananthakrishnan; Ann      Marie Schmidt; Ravichandran      Ramasamy

Abstract

Cardiovascular disease represents the major cause of morbidity and mortality in patients with diabetes mellitus. Studies by us and others have implicated increased flux via aldose reductase (AR) as a key player in mediating diabetic complications, including cardiovascular complications. Data suggest that increased flux via AR in diabetics perpetuates increased injury after myocardial infarction, accelerates atherosclerotic lesion formation, and promotes restenosis via multiple mechanisms. Most importantly, studies have shown that increased generation of reactive oxygen species due to flux via AR has been a common feature in animal models of diabetic cardiovascular disease. Taken together, these considerations place AR in the center of biochemical and molecular stresses that characterize the cardiovascular complications of diabetes. Stopping AR-dependent signaling may hold the key to interrupting cycles of cellular perturbation and tissue damage in diabetic cardiovascular complications.

Keywords: Advanced glycation end products, Aldose reductase, Aldose reductase inhibitors, atherosclerosis, cardiovascular complications, Diabetes, hyperglycemia, ischemia reperfusion, Oxidative stress, Polyol pathway