Mechanisms regulating hepatic SR-BI expression and their impact on HDL metabolism

Andrea Leiva, Hugo Verdejo, María Luisa Benítez, Alvaro Martínez, Dolores Busso, Attilio Rigotti

Research output: Contribution to journalScientific reviewpeer-review

49 Scopus citations

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.
Original languageAmerican English
Pages (from-to)299-307
Number of pages9
JournalAtherosclerosis
Volume217
Issue number2
DOIs
StatePublished - 1 Aug 2011
Externally publishedYes

Keywords

  • Atherosclerosis
  • Bile
  • HDL
  • Hepatic SR-BI expression
  • Reverse cholesterol transport
  • SR-BI

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