The Renin-Angiotensin system and vascular disease in diabetes

Angiotensin II, the effector molecule of the renin-angiotensin system, has profound effects on endothelial and smooth muscle cells. These effects are not only hemodynamic in nature, but also comprise inflammation, thrombosis, and cell proliferation through stimulation of production of cytokines and growth factors. In diabetes mellitus these effects seem amplified with adverse consequences like atherosclerosis and occlusive microangiopathy. Suggestive evidence for this notion is the impressive beneficial effect of pharmacological interference with the renin-angiotensin system in large vessel disease as well as in renal and retinal microangiopathy. Since the circulating renin-angiotensin system does not seem to be activated in diabetes mellitus it is now thought that independent tissue renin-angiotensin systems play a role in diabetic complications. Whether any genetic propensity to diabetic angiopathy resides in genes of the renin-angiotensin system remains to be determined.