The role of endothelium in the pathogenesis of diabetic microangiopathy.

Damage caused to the vessel wall by diverse mechanisms may lead to diabetic microangiopathy. Consequently, research work is more and more focusing on the pathophysiology of vascular cells, with particular emphasis on endothelium. This paper reviews the present knowledge on the alterations of small vessel endothelium in diabetes. The most important risk factors for diabetic microangiopathy are the duration of disease and the degree of metabolic control maintained throughout the years. However, genetic factors may also contribute. These are examined first, followed by the presumed roles played by increased protein glycation and the production of Advanced Glycosylation End Products, the "polyol pathway" and free radical generation. Endothelium is a widespread, extremely active organ which regulates complex physiologic functions and its structure and function are discussed in the second section of this review. The third part deals with how diabetes can affect endothelium and describes observations on endothelial metabolism in vitro as well as morphologic and functional alterations in the patients. Unfortunately, the mechanisms leading to progressive degeneration of the microcirculation and organ damage in diabetic patients remain largely unaccounted for.