Scavenger Receptor Class B Type I–Mediated Protection Against Atherosclerosis in LDL Receptor–Negative Mice Involves Its Expression in Bone Marrow–Derived Cells

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Abstract
Objective— Scavenger receptor class B type I (SR-BI) is a cell-surface HDL receptor that is implicated in reverse cholesterol transport and protection against atherosclerosis. We have previously demonstrated that SR-BI/apolipoprotein E double-knockout mice develop severe occlusive coronary artery disease and myocardial infarction and die at ≈6 weeks of age. To determine if this is a general effect of a lack of SR-BI, we generated mice deficient in both SR-BI and the LDL receptor. Methods and Results— Complete ablation of SR-BI expression in LDL receptor knockout mice resulted in increased plasma cholesterol associated with HDL particles of abnormally large size and a 6-fold increase in diet-induced aortic atherosclerosis but no macroscopic evidence of early-onset coronary artery disease, cardiac pathology, or early death. Furthermore, selective elimination of SR-BI expression in bone marrow–derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant a...