Scavenger receptor class B type I in high-density lipoprotein metabolism, atherosclerosis and heart disease: lessons from gene-targeted mice.
The scavenger receptor class B type I (SR-BI) is a multi-ligand receptor that can mediate the binding and bi-directional lipid transfer between high-density lipoproteins (HDLs) and cells. It is expressed in a variety of tissues, including the liver, and in macrophages in atherosclerotic plaques. The physiological role of SR-BI has been tested in vivo by the genetic manipulation of SR-BI levels in mice. Mice lacking SR-BI exhibit impaired hepatic-selective HDL cholesterol uptake and increased atherosclerosis, suggesting that SR-BI is required for hepatic reverse cholesterol transport and normally protects against atherosclerosis. Surprisingly, elimination of SR-BI in apolipoprotein E knockout mice results in rapid development of occlusive coronary artery disease, accompanied by spontaneous myocardial infarction, reduced heart function and early death, which points to a role for SR-BI in protection against coronary heart disease. The in vivo role of macrophage SR-BI has been less clear. We have used bone-marrow transplantation to demonstrate that bone-marrow-derived SR-BI also normally protects against atherosclerosis in low-density lipoprotein receptor knockout mice. These results suggest that SR-BI may have multiple protective effects against atherosclerosis in different tissues.
Trigatti
B
B
Department of Biochemistry, McMaster University, 1200 Main St West, Hamilton, ON, Canada L8N 3Z5. trigatt@mcmaster.ca
Covey
S
S
Rizvi
A
A
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens; D003324:Coronary Artery Disease / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D051379:Mice; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D001055:Apolipoproteins B; D018955:CD36 Antigens; D008075:Lipoproteins, HDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B