Tetsuya Hayashi, Shinji Takai and Chika Yamashita Pages 189 - 197 ( 9 )
Diabetes mellitus is a leading cause of morbidity and mortality because of its cardiovascular complications. It has been suggested that hyperglycemia, hyperinsulinemia and insulin resistance, glycation of proteins, oxidative stress, inflammation, and many other factors may be related to atherogenesis in diabetes. The metabolic abnormalities associated with diabetes lead to activation of the renin-angiotensin-aldosterone-system (RAAS), with a subsequent increase of angiotensin II and aldosterone levels, which might alter the insulin signaling pathway and promote the formation of reactive oxygen species that induce endothelial dysfunction as well as cardiovascular disease and renal disease. Synthesis of angiotensin II is not only catalyzed by angiotensin-converting enzyme, but also by chymase. Recently, angiotensin II produced by chymase was reported to be involved in vascular proliferation and atherosclerosis. Chymase also activates matrix metalloproteinase- 9, leading to extracellular matrix degradation, and promotes cardiovascular remodeling. Many studies have shown that angiotensin-II blockade significantly reduces the levels of proinflammatory mediators and suppresses oxidative stress. In clinical trials, RAAS blockade has been found to delay or prevent the onset of type 2 diabetes, and it also prevents cardiovascular and renal events in diabetic patients. Thus, RAAS inhibition represents first-line treatment for hypertensive and diabetic target organ damage, as well as preventing the progression of cardiovascular disease and kidney disease. This review presents the available information about the role of the RAAS in the cardiovascular and renal complications of diabetes.
Diabetes mellitus, renin-angiotensin-aldosterone-system, chymase, heart, kidney, oxidative stress
Department of Internal Medicine III, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 569-8686, Japan.