Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on cholesterol levels and atherosclerosis in ApoE-deficient mice

In the arterial wall, scavenger receptor class A (SRA) is implicated in pat hological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified Lipoproteins from the circulation, thereby protecting the b ody from their pathological action. The role of SRA on bone marrow-derived cells in lipid metabolism and atherogenesis was assessed in vivo by transpl antation of bone marrow cells overexpressing human SRA (MSR1) to apoE-defic ient mice. In vitro studies with peritoneal macrophages from the transplant ed mice showed that macrophage scavenger receptor function, as measured by cell association and degradation studies with acetylated LDL, was approxima te to3-fold increased on overexpression of MSR1 in bone marrow-derived cell s as compared with control mice. Despite the increased macrophage scavenger receptor function in vitro, no significant effect of MSRI overexpression i n bone marrow-derived cells on the in vivo atherosclerotic lesion developme nt was found. In addition to arterial wall macrophages, liver sinusoidal Ku pffer cells also overexpress MSRI after bone marrow transplantation, which may scavenge atherogenic particles more efficiently from the blood compartm ent. Introduction of bone marrow cells over expressing human MSR1 in apoE-d eficient mice induced a significant reduction in serum cholesterol levels o f approximate to 20% (P<0.001, 2-way ANOVA) as the result of a decrease in VLDL cholesterol. It is suggested that the reduction in VLDL cholesterol le vels is due to increased clearance of modified Lipoproteins by the overexpr essed MSR1 in Kupffer cells of the liver, thereby protecting the arterial w all against the proatherogenic action of modified lipoproteins.