418 Expression of SR-BI in Bone Marrow Derived Cells Protects Against Diet-Induced Coronary Artery Atherosclerosis in SR-BI−/−apoE-R61-Hypomorphic Mice

Abstract

Mice deficient in the HDL receptor SR-BI with mutant apolipoproteinE(apoE) develop occlusive coronary artery atherosclerosis, myocardial infarction and premature death. They can be rescued by transplantation of wild type bone marrow. However, it is unknown if the protection of wild type bone marrow depends on the contributions of SR-BI, apoE or both. Here, we used bone marrow transplantation into SR-BI−/−apoE-R61h/h recipients to test if restoration of either SR-BI or ApoE alone was sufficient to protect against either aortic sinus or diet-induced CA atherosclerosis. Transplantation of bone marrow from SR-BI+/+apoE-R61h/h mice into SR-BI−/−apoE-R61h-h recipients generated mice expressing SR-BI exclusively in bone marrow-derived cells. This prevented the development of diet-induced occlusive CA atherosclerosis and myocardial infarction. In contrast, mice transplanted with autologous bone marrow or with bone marrow from SR-BI−/−/apoE+/+ mice (allowing restoration of normal apoE expression in bone marrow-derived cells) were not protected from occlusive coronary artery atherosclerosis and myocardial infarction. To test the mechanism involved, we compared the recruitment of leukocytes into the atherosclerotic vessels in SR-BI−/−apoE-R61h/h and SR-BI+/+apoE-R61h/h mice. Our results indicate that restoration of SR-BI in bone marrow-derived cells is sufficient to prevent occlusive coronary artery atherosclerosis in SR-BI−/−apoE-R61h/h mice and indicate an important role for SR-BI in BM-derived cells in protection against atherosclerosis. CIHR