SR-BI deficient mice that are also hypomorphic for
apolipoprotein E expression develop diet induced occlusive coronary artery
atherosclerosis,
myocardial infarction and early death. To test the role of SR-BI in bone marrow derived cells, we used
bone marrow transplantation to generate SR-BI-null;
apoE-hypomorphic mice in which SR-BI expression was restored solely in bone marrow derived cells. SR-BI-null;
apoE-hypomorphic mice were transplanted with SR-BI(+/+)
apoE-hypomorphic, or control, autologous SR-BI-null;
apoE-hypomorphic bone marrow. Four weeks later, mice were fed a high-fat, high-
cholesterol,
cholate-containing diet to induce coronary artery
atherosclerosis. Mice transplanted with autologous bone marrow developed extensive aortic
atherosclerosis and severe occlusive coronary artery
atherosclerosis after 4 weeks of feeding. This was accompanied by myocardial
fibrosis and increased heart weights. In contrast, restoration of SR-BI expression in bone marrow derived-cells reduced diet induced aortic and coronary artery
atherosclerosis, myocardial
fibrosis and the increase in heart weights in SR-BI-null;
apoE-hypomorphic mice. Restoration of SR-BI in bone marrow derived cells did not, however, affect steady state
lipoprotein cholesterol levels, but did reduce plasma levels of
IL-6. Monocytes from SR-BI-null mice exhibited a greater capacity to bind to
VCAM-1 and
ICAM-1 than those from SR-BI(+/+) mice. Furthermore, restoration of SR-BI expression in bone marrow derived cells attenuated monocyte recruitment into
atherosclerotic plaques in mice fed high fat, high
cholesterol cholate containing diet. These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and CA
atherosclerosis.