Purpose: To reconstruct the role played by vascular endothelium in the elevation of circulating von Willebrand factor (vWf) in diabetic patients with microangiopathy and, specifically, to determine whether storage and synthesis of vWf is altered in diabetic retinal vessels.
Methods: Trypsin digests were prepared from retinas obtained post mortem from 11 patients (age 62 +/- 9 years, mean +/- SD) with 9 +/- 5 years of diabetes and 12 nondiabetic control subjects matched for age and sex. Trypsin digests were inspected for the presence of lesions of diabetic retinopathy; vWf protein was localized by indirect immunofluorescence; and vWf mRNA levels were studied by in situ hybridization.
Results: vWf immunofluorescence was present in vessels of all sizes. The granular fluorescence was localized to the endothelial cell cytoplasm. Pattern and intensity of staining in diabetic microvessels and large vessels were similar to those observed in the vessels of nondiabetic subjects. The amount of vWf mRNA detected by in situ hybridization in retinal endothelial cells was similar in diabetic (0.92 +/- 0.32 grains/cell) and control (0.91 +/- 0.42 grains/cell) microvessels. Likewise, no differences were observed in vWf mRNA levels in the large vessels of diabetic (0.073 +/- 0.034% grain area) and control (0.069 +/- 0.018 grain area) subjects.
Conclusions: These observations are compatible with the occurrence in diabetes of the slow release of endothelial vWf through the pathway of vWf secretion not linked to synthesis, ie, the regulated pathway.