Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knockout mice

Scavenger receptors, which include various classes, play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoprote ins, resulting in the massive accumulation of cholesteryl esters. Because m acrophage-derived foam cells are considered to be an important feature in e arly atherogenesis, we investigated the role of scavenger receptor class A (SR-A) overexpression, especially on macrophages in lipoprotein metabolism and atherosclerosis. Bone marrow from human SR-A (MSR1)-overexpressing mise was transplanted into irradiated low density Lipoprotein receptor knockout [LDLR(-/-)] mice. The transplantation resulted in an increase in total ser um cholesterol (approximately 15 to 25%), especially in the VLDL fraction, when compared with LDLR(-/-) mice that were transplanted with bone marrow o f wild-type littermates. Quantification of atherosclerotic lesions in the m ice that were fed a "Western-type" diet for 3 months revealed that there we re no differences in mean lesion area between LDLR(-/-) mice transplanted w ith MSR1 overexpressing and wild-type Littermate bone marrow, despite incre ased scavenger receptor activity in vitro. The presence or absence of the L DLR in the transplanted bone marrow did not influence these results,SIP In conclusion, introduction of MSR1-overexpressing bone marrow in LDLR(-/-) mi ce via bone marrow transplantation resulted in a slight increase in lipopro tein levels, but had no effect on the atherosclerotic lesion area, despite increased scavenger receptor activity in vitro.-Herijgers, N., M. P. J. de Winther. M. Van Eck. L. M. Havekes, M. H. Hofker, P. M. Hoogerbrugge, and T . J. C. Van Berkel. Effect of human scavenger receptor class A overexpressi on in bone marrow-derived cells on lipoprotein metabolism and atheroscleros is iu low density lipoprotein receptor knock-out mice.