Aortic endothelial cell von Willebrand factor content, and circulating plasminogen activator inhibitor-1 are increased, but expression of endothelialleukocyte adhesion molecules is unchanged in insulin-dependent diabetic BBrats

Endothelial cell injury has been implicated in the increased incidence of v ascular disease associated with diabetes mellitus. In diabetic humans, elev ated plasma von Willebrand Factor (VWF) has been interpreted as an indicati on of endothelial damage. In contrast, in an animal model of inherited insu lin-dependent diabetes, the bio-breeding (BB) rat, plasma VWF levels did no t differ from those in age-matched control rats during the first 7 months o f diabetes although morphological evidence of mild aortic endothelial alter ation or injury was observed. In the present study efforts have been made t o define the endothelial alterations in BE diabetic rats compared to contro ls more precisely over this time period. Thus, adhesion molecules: intercel lular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VC AM-1) were evaluated by in situ immunohistochemistry, vWF content was deter mined by biochemical analysis of aortic extracts and by quantitative immuno histochemistry, plasma VWF levels were measured by ELISA and vWF mRNA by RN Ase protection assay. Neither age nor diabetic state significantly affected either the expression of adhesion molecules, or the levels of circulating vWF. Endothelial VWF content was significantly increased in the diabetic ve ssels, as observed by both approaches but the vWF mRNA content was not diff erent from that in control vessels. Plasma plasminogen activator inhibitor (PAI-1) activity was significantly increased in diabetic animals. In conclu sion, endothelial alterations in BE rats associated with diabetes, together with the raised plasma PAI-I levels, promote the thrombogenic potential of the vessel wall, and are consistent with an increased risk for vascular di sease. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.