SR-BI in bone marrow derived cells protects mice from diet induced coronary artery atherosclerosis and myocardial infarction.

Abstract

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.

• Authors: Ying Pei, Xing Chen, Dina Aboutouk, Mark T Fuller, Omid Dadoo, Pei Yu, Elizabeth J White, Suleiman A Igdoura, Bernardo L Trigatti
• Journal: PloS one (PLoS One) Vol. 8 Issue 8 Pg. e72492 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23967310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• CD36 Antigens
• Inflammation Mediators
• Lipids
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Aorta (pathology)
• Apolipoproteins E (deficiency)
• Bone Marrow Cells (metabolism)
• Bone Marrow Transplantation
• CD36 Antigens (genetics, metabolism)
• Coronary Artery Disease (genetics, pathology, therapy)
• Coronary Vessels (metabolism, pathology)
• Diet
• Disease Models, Animal
• Female
• Fibrosis
• Inflammation Mediators (blood, metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Lipids (blood)
• Male
• Mice
• Mice, Knockout
• Monocytes (immunology, metabolism)
• Myocardial Infarction (genetics, therapy)
• Myocardium (pathology)
• Organ Size
• Vascular Cell Adhesion Molecule-1 (metabolism)