Abstract 669: SR-BI in Bone Marrow--Derived Cells Protects Mice From Diet-Induced Coronary Artery Atherosclerosis and Myocardial Infarction
Background: SR-BI deficient, apolipoprotein E hypomorphic mice develop diet induced occlusive coronary artery atherosclerosis, myocardial infarction and early death.
Methods: To test the role of SR-BI 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.
Results: 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 reduced 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.
Conclusion: These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and coronary artery atherosclerosis.
Author Disclosures: Y. Pei: None. X. Chen: None. D. Aboutouk: None. M.T. Fuller: None. O. Dadoo: None. P. Yu: None. E.J. White: None. S. Igdoura: None. B.L. Trigatti: None.
- © 2014 by American Heart Association, Inc.