vonWillebrand factor (vWf) as a plasma marker of endothelial activation indiabetes: Improved reliability with parallel determination of the vWf propeptide (vWf : AgII)

Elevated plasma von Willebrand factor (vWf) levels are found in diabetes an d other vasculopathies, and predict cardiovascular mortality. vWf is stored and released from endothelial cell secretory granules, along with equimola r amounts of its propeptide (vWf:AgII). In the present study, we examined p lasma propeptide levels as a marker of endothelial secretion in vivo, using an ELISA based on monoclonal antibodies. vWf but not propeptide levels are influenced by blood groups, explaining in part the smaller variation in pl asma propeptide levels among normal individuals. In both controls and insul in-dependent diabetic patients, we found a close correlation between propep tide and immunoreactive vWf levels (r(2) = 0.54, p <0.0001). vWf and propep tide were elevated in patient subgroups with microalbuminuria or overt diab etic nephropathy, whereas only the propeptide was significantly elevated in the normoalbuminuric subgroup. This observation suggests that in conjuncti on with vWf, propeptide measurements may improve the identification of endo thelial activation, which occurs frequently even without increased urinary albumin excretion. In 12 NIDDM patients, a 3-week diet enriched in monounsa turated fat (MUFA) resulted in parallel decreases in vWf (-22%, p < 0.05) a nd propeptide (-17%, p < 0.05) levels, indicating that the experimental die t affected endothelial secretion rather than vWf catabolism. A carbohydrate -enriched control diet did not significantly influence either marker. Our results suggest that concomittant determinations of plasma vWf and prop eptide are useful tools to assess endothelial activation in vivo, and reinf orce our previous conclusion that a diet rich in MUFA can improve endotheli al function in NIDDM.