Endothelial cell dysfunction and the pathogenesis of diabetic macroangiopathy

Type 2 diabetes mellitus (DM) represents a high risk condition for the deve lopment of atherosclerotic and thromboembolic macroangiopathy, which make m ajor contributions to diabetic mortality and morbidity. While many cardiova scular risk factors are common to both atherosclerosis and Type 2 DM, the e nhanced risk of diabetic macroangiopathy may be attributable to additional pro-atherogenic mediators associated with insulin resistance syndrome. Give n the central pathogenic role of endotheliopathy in atherosclerosis, it is likely that this vascular monolayer is the ultimate target of injury in res ponse to such mediators. Furthermore, a pro-oxidative, dysfunctional endoth elium may actively contribute to the pro-atherogenic environment through an inappropriate regulation of vascular tone, permeability, coagulation, fibr inolysis, cell adhesion and proliferation. Such dysfunction may mediate hyp ertension, dyslipidaemia and altered haemostasis, in addition to aggravatin g in vivo insulin resistance. Copyright (C) 1999 John Wiley a Sons, Ltd.