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 HDL(3) 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 HDL(3) to promote cholesterol efflux from human macrophage foam cells. After exposure to plasmin or plasma kallikrein for 15 min, HDL(3) showed a decrease of about 60% in its ability to promote cholesterol efflux from the macrophage foam cells. SDS-PAGE analysis of the degraded HDL(3) 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 HDL(3) particles. Agarose gel electrophoresis showed that a decrease in cholesterol efflux was accompanied by total loss of the HDL(3) with prebeta-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.
Lindstedt
L
L
Wihuri Research Institute, Kalliolinnatie 4, Helsinki, 00140, Finland.
Kovanen
P T
PT
D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D003029:Coagulants / Q000494:pharmacology; D005341:Fibrinolysin / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism*
D003029:Coagulants; D005343:Fibrinolytic Agents; D008075:Lipoproteins, HDL; D002784:Cholesterol; D007610:Kallikreins; D005341:Fibrinolysin