Effects of heparin-mediated extracorporeal low-density lipoprotein precipitation beyond lowering proatherogenic lipoproteins--reduction of circulating proinflammatory and procoagulatory markers.

ABSTRACT

In addition to hypercholesterolemia, proinflammatory and prothrombotic markers have been suggested to play an important role in atherogenesis. We examined whether heparin-mediated extracorporeal low-density lipoprotein precipitation (HELP) therapy modulates the circulating levels of proinflammatory and prothrombotic markers. Twenty-two coronary heart disease (CHD) patients undergoing regular HELP-apheresis (18 males, 4 females, mean age 57.3 +/- 10.9 years) were enrolled in this study. A single HELP therapy treatment significantly decreased the circulating levels of high sensitivity C-reactive protein (hs-CRP), soluble vascular adhesion molecule-1 (sVCAM-1), soluble E-selectin, lipopolysaccharide binding protein (LBP), endothelin-1 (ET-1), and monocyte chemoattractant protein-1 (MCP-1) on average by 67, 37, 24, 27, 24, and 15%, respectively. Prothrombotic factors including fibrinogen, tissue factor (TF), soluble CD40 ligand (sCD40L), and homocysteine were decreased by 66, 27, 16, and 22%, respectively. In accordance with previous studies HELP therapy reduced total cholesterol, low density lipoprotein (LDL) cholesterol, and Lp(a) mass by 50, 61, and 62%, respectively. Our data suggest that simultaneous reduction of proinflammatory and prothrombotic factors together with atherogenic lipoproteins by HELP-apheresis may contribute to improvement of endothelial dysfunction and thereby inhibit progression of atherosclerotic lesions and stabilize the existing plaque.