Release of endothelium-associated proteins into blood by injection of heparin in normal subjects and in patients with Type 1 diabetes.

Abstract

Disturbances in heparan sulphate proteoglycans in patients with diabetic nephropathy might contribute to the pathogenesis of vascular disease in these patients. To investigate this possible link, we measured the heparin-induced, immediate release of eight proteins with heparan sulphate binding properties in patients with nephropathy. We studied three groups, Type 1 diabetic patients with (n = 10) or without (n = 15) albuminuria and matched controls (n = 12). Blood samples were obtained before and 5 min after the injection of 40 anti-Xa IU low molecular weight heparin/kg body weight. Lipoprotein lipase increased more in diabetic patients without albuminuria than in controls and patients with albuminuria [261 (170-293) vs. 177 (103-438), P < 0.05 and 203 (159-280) mU/ml, P < 0.05]. Total tissue factor pathway inhibitor increased more in the diabetic patients [284 (198-449) and 275 (243-399)] than in the controls [221 (169-289) ng/ml, P < 0.005]. Vitronectin increased significantly only in the diabetic patients with albuminuria. The remaining proteins did not increase significantly (antithrombin, von Willebrand factor, fibronectin) or increased equally in the three investigated groups (extracellular superoxid dismutase and platelet factor 4). The different release of lipoprotein lipase and vitronectin in diabetic subjects with and without albuminuria may reflect novel aspects of vascular derangement in patients with albuminuria.