Plasmin and kallikrein reduce HDL-induced cholesterol efflux from foam cells

Arterial intima contains metabolically active factors such as proteases, which may act on high-density lipoprotein (HDL) and impair its ability to accept cholesterol. In this study we treated human HDL3 with human plasmin and human plasma kallikrein, two proteases also found in the human arterial intima, in order to study their effect on the ability of HDL3 to promote cholesterol efflux from human macrophage foam cells. After exposure to plasmin or plasma kallikrein for 15 min, HDL3 showed a decrease of about 60% in its ability to promote cholesterol efflux from the macrophage foam cells. SDS-PAGE analysis of the degraded HDL3 particles showed that plasmin had generated cleavage products less than 15 kDa in size and plasma kallikrein had generated a major product of about 19 kDa. However, there was only a slight loss of intact apolipoproteins, suggesting degradation of a small subpopulation of HDL3 particles. Agarose gel electrophoresis showed that a decrease in cholesterol efflux was accompanied by total loss of the HDL3 with pre beta -mobility, but no apparent change in those with alpha mobility. These results suggest that the presence of active plasmin or plasma kallikrein in the atherosclerotic arterial intima promotes atherogenesis by blocking cholesterol efflux from macrophage foam cells. (C) 2000 Academic Press.