Published online before print August 14, 2003, doi: 10.1161/01.ATV.0000091363.28501.84
© 2003 American Heart Association, Inc.
Brief Reviews |
Influence of the HDL Receptor SR-BI on Lipoprotein Metabolism and Atherosclerosis
From the Department of Biochemistry (B.L.T.), McMaster University, Hamilton, Ontario, Canada; Biology Department (M.K.), Massachusetts Institute of Technology, Cambridge, Mass; and Departamento de Gastroenterología (A.R.), Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Correspondence to Dr A. Rigotti, Departmento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Marcoleta 367, Santiago, Chile. E-mail arigotti{at}med.puc.cl
Series Editor: James Scott
ATVB in Focus
Lipoproteins, Inflammation, and Atherosclerosis
Previous Brief Reviews in this Series:
•Pennachhio LA, Rubin EM. Apolipoprotein A5, a newly identified gene that affects plasma triglyceride levels in humans and mice. 2003;23:529–534.
•Cullen P, Baetta R, Bellosta S, Bernini F, Chinetti G, Cignarella A, von Eckardstein A, Exley A, Goddard M, Hofker M, Hurt-Camejo E, Kanters E, Kovanen P, Lorkowski S, McPheat W, Pentikäinen M, Rauterberg J, Ritchie A, Staels B, Weitkamp B, de Winther M for the MAFAPS Consortium. Rupture of the atherosclerotic plaque: does a good animal model exist? 2003;23:535–542.
•Allayee H, Ghazalpour A, Lusis AJ. Using mice to dissect genetic factors in atherosclerosis. 2003;23:1501–1509.
•Calabresi L, Gomaraschi M, Franceschini G. Endothelial protection by high-density lipoproteins: from bench to bedside. 2003;23:1724–1731.
The scavenger receptor class B type I (SR-BI) was the first molecularly well-defined cell-surface HDL receptor to be described. SR-BI mediates selective HDL cholesterol uptake by formation of a productive lipoprotein/receptor complex, which requires specific structural domains and conformation states of apolipoprotein A-I present in HDL particles. SR-BI is abundantly expressed in several tissues, including the liver, where its expression is regulated by various mechanisms, including the transcriptional activity of nuclear receptors. The importance of SR-BI in overall HDL cholesterol metabolism and its antiatherogenic activity in vivo has been definitively established by SR-BI gene manipulation in mice. Remarkably, SR-BI/apolipoprotein E double-knockout mice develop complex coronary artery disease, myocardial infarction, and heart failure. Additional studies should help to define the importance of SR-BI in human health and disease.
Key Words: scavenger receptor class B type I • selective uptake • regulation • knockout mouse • coronary heart disease
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