DEFENSIN STIMULATES THE BINDING OF LIPOPROTEIN (A) TO HUMAN VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS

There is evidence to suggest that elevated plasma levels of lipoprotei n (a) [Lp(a)] represent a risk factor for the development of atheroscl erotic vascular disease, but the mechanism by which this lipoprotein l ocalizes to involved vessels is only partially understood. In view of studies suggesting a link between inflammation and atherosclerosis and our previous finding that leukocyte defensin modulates the interactio n of plasminogen and tissue-type plasminogen activator with cultured h uman endothelial cells, we examined the effect of this peptide on the binding of Lp(a) to cultured vascular endothelium and vascular smooth muscle cells. Defensin increased the binding of Lp(a) to endothelial c ells approximately fourfold and to smooth muscle cells approximately s ixfold. Defensin caused a comparable increase in the amount of Lp(a) i nternalized by each cell type, but Lp(a) internalized as a consequence of defensin being present was not degraded, resulting in a marked inc rease in the total amount of cell-associated lipoprotein. Abundant def ensin was found in endothelium and in intimal smooth muscle cells of a therosclerotic human cerebral arteries, regions also invested with Lp( a). These studies suggest that defensin released from activated or sen escent neutrophils may contribute to the localization and persistence of Lp(a) in human vessels and thereby predispose to the development of atherosclerosis. (C) 1997 by The American Society of Hematology.