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Biochemical Society Transactions (2004) 32, (116–120) (Printed in Great Britain)

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Scavenger receptor class B type I in high-density lipoprotein metabolism, atherosclerosis and heart disease: lessons from gene-targeted mice

B. Trigatti¹, S. Covey and A. Rizvi

Department of Biochemistry, McMaster University, 1200 Main St West, Hamilton, ON, Canada L8N 3Z5

Key words: atherosclerosis, cholesterol, high-density lipoprotein (HDL), lipoprotein, scavenger receptor class B type I (SR-BI), transgenic.

Abbreviations used: ABC, ATP-binding cassette transporter; Apo, apolipoprotein; HDL, high-density lipoprotein; LDL, low-density lipoprotein; SR-BI, scavenger receptor class B type I; VLDL, very-low-density lipoprotein.

¹To whom correspondence should be addressed (e-mail trigatt@mcmaster.ca).

Abstract

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.

Received 7 September 2003

© 2004 Biochemical Society