title: Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism.
abstract: High-density lipoproteins (HDLs) are major carriers of cholesterol in the bloodstream and are critical in regulating cholesterol homeostasis in vivo. The first molecularly well-defined and physiologically relevant HDL receptor to be characterized was the scavenger receptor class B type I (SR-BI), a cell surface glycoprotein most highly expressed in liver and steroidogenic tissues. The HDL receptor SR-BI plays a key role in mediating selective HDL cholesterol (HDL-C) uptake in the liver, thus controlling cholesterol levels in plasma and the transhepatic traffic of this lipid into bile. SR-BI knockout mice exhibit increased plasma HDL-C levels and abnormally large HDL particles as well as reduced biliary cholesterol levels. Conversely, transgenic mice overexpressing SR-BI in the liver have markedly reduced plasma HDL levels, accelerated HDL-C clearance, increased hepatic selective cholesterol uptake, and raised biliary cholesterol content. The regulation of HDL-C metabolism by hepatic SR-BI is relevant for cardiovascular health as shown in mouse models where the lack of this receptor in the liver induces atherosclerotic lesions, whereas hepatic SR-BI overexpression entails a reduction of atherosclerosis. This review summarizes some recent progress in understanding the mechanisms that regulate hepatic SR-BI expression at transcriptional and post-transcriptional levels, providing opportunities for novel approaches that may improve HDL-dependent cholesterol homeostasis and lead to better prevention and treatment of atherosclerosis in humans.
authors: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors: Andrea
authors: A
authors: Leiva
authors: Hugo
authors: H
authors: Verdejo
authors: María Luisa
authors: ML
authors: Benítez
authors: Alvaro
authors: A
authors: Martínez
authors: Dolores
authors: D
authors: Busso
authors: Attilio
authors: A
authors: Rigotti
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL