Evidence that endogenous heparin activity deficiency may be an important factor in atherogenesis

Known atherosclerotic risk factors account today for only 50% of atherogenesis. Evidence is presented that a deficiency of endogenous heparin may account for the other half. Sensitive techniques have shown that there are trace quantities of heparin in plasma of humans. An inverse relationship has been found between plasma heparin levels and triglyceride-bearing Sf 12-400 lipoprotein, and a lower plasma heparin level could be an important determinant of atherogenesis fostering lipid abnormalities. Endogenous heparin also protects endothelium from harmful mediators that can impair normal function. Since atherosclerosis is a chronic inflammatory disease process, with monocyte-mediated release of cytokines and activation of integrins and phospholipase A2-mediated generation of platelet activating factor, heparin inhibits many of these events. Endogenous heparin activity thus opposes the effects of inflammatory activators. Heparin is also kown to inhibit complement activation and to suppress endothelin release from endothelial cells. In addition, endogenous heparin may suppress smooth muscle cell proliferation and decrease microthrombi formation on injured endothelial sites. All of these data seem to suggest that a deficiency of endogenous heparin or heparin-like substances predipose to atherosclerosis. It is conceivable that a genetically determined endogenous heparin deficiency is involved in atherosclerosis.