VASCULAR WALL VON-WILLEBRAND-FACTOR IN HUMAN DIABETIC-RETINOPATHY

Purpose. To reconstruct the role played by Vascular endothelium in the elevation of circulating von Willebrand factor (vWf) in diabetic pati ents with microangiopathy and, specifically, to determine whether stor age and synthesis of vWf is altered in diabetic retinal vessels. Metho ds. Trypsin digests were prepared form retinas obtained post mortem fr om II 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 diabeti c retinopathy; vWf protein was localized by indirect immunofluorescenc e; and vWf mRNA levels were studied by in situ hybridization. Results. vWf immunofluorescence was present in vessels of all sizes. The granu lar fluorescence was localized to the endothelial cell cytoplasm. Patt ern and intensity of staining in diabetic microvessels and large vesse ls were similar to those observed in the vessels of nondiabetic subjec ts. The amount of vWf mRNA detected by in situ hybridization in retina l endothelial cells was similar in diabetic (0.92 +/- 0.32 grains/cell ) and control (0.91 +/- 0.42 grains/cell) microvessels. Likewise, no d ifferences were observed in vWf mRNA levels in the large vessels of di abetic (0.073 +/- 0.034% grain area) and control (0.069 +/- 0.018 grai n area) subjects. Conclusions. These observations are compatible with the occurrence in diabetes of the slow release of endothelial vWf thro ugh the pathway of vWf secretion not linked to synthesis, ie, the regu lated pathway.