Changes in the aortic endothelium and plasma von Willebrand factor levels during the onset and progression of insulin-dependent diabetes in BB rats

Abstract

Endothelial injury has been implicated in the enhanced vascular disease associated with diabetes mellitus. In diabetic humans elevated plasma von Willebrand factor (vWF) levels have been interpreted as an indication of endothelial damage. Using the BB rat as a model of inherited insulin dependent-diabetes mellitus, plasma vWF and aortic endothelial ultrastructural alterations were examined during the first 7 months of diabetes. Total plasma vWF levels were determined by ELISA and vWF multimeric composition by electrophoresis. vWF was identified immunohistochemically. Following the onset of hyperglycemia, there were progressive alterations in aortic endothelial morphology, which were consistent with injury, and aortic intimal thickening was significantly greater in rats diabetic for 7 months compared to age-matched controls. Significant increases in the Weibel Palade (WP) body content of the endothelial cells were observed after 1 week and 2 months of diabetes, but not at later times. Endothelial alterations associated with the possible release of vWF appeared to involve fusion of WP bodies with other vacuoles rather than direct fusion with the cell membrane. Plasma vWF levels in diabetic rats were varied, but were not significantly different from those of control animals and did not correlate with either glucose or insulin levels. The multimeric composition of plasma vWF was also similar at all times in both diabetic and non-diabetic animals. From these observations, plasma vWF levels do not provide an indicator of the endothelial perturbations which occurs in diabetic rats.