Intestinal cholesterol transport proteins: an update and beyond.
OBJECTIVE
Various studies have delineated the causal role of dietary cholesterol in atherogenesis. Strategies have thus been developed to minimize cholesterol absorption, and cholesterol transport proteins found at the apical membrane of enterocytes have been extensively investigated. This review focuses on recent progress related to various brush-border proteins that are potentially involved in alimentary cholesterol transport.


RESULTS
Molecular mechanisms responsible for dietary cholesterol and plant sterol uptake have not been completely defined. Growing evidence, however, supports the concept that several proteins are involved in mediating intestinal cholesterol transport, including SR-BI, NPC1L1, CD36, aminopeptidase N, P-glycoprotein, and the caveolin-1/annexin-2 heterocomplex. Other ABC family members (ABCA1 and ABCG5/ABCG8) act as efflux pumps favoring cholesterol export out of absorptive cells into the lumen or basolateral compartment. Several of these cholesterol carriers influence intracellular cholesterol homeostasis and are controlled by transcription factors, including RXR, LXR, SREBP-2 and PPARalpha. The lack of responsiveness of NPC1L1-deficient mice to ezetimibe suggests that NPC1L1 is likely to be the principal target of this cholesterol-lowering drug.


CONCLUSIONS
The understanding of the role, genetic regulation and coordinated function of proteins mediating intestinal cholesterol transport may lead to novel ways of treating cardiovascular disease.
Levy
Emile
E
Research Centre, CHU-Sainte-Justine, Québec, Canada. emile.levy@recherche-ste-justine.qc.ca
Spahis
Schohraya
S
Sinnett
Daniel
D
Peretti
Noel
N
Maupas-Schwalm
Françoise
F
Delvin
Edgard
E
Lambert
Marie
M
Lavoie
Marc-André
MA
D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism; D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000378:metabolism; D004032:Diet; D006801:Humans; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D013261:Sterols / Q000737:chemistry
C472822:ANXA2 protein, human; D017306:Annexin A2; D000924:Anticholesteremic Agents; D018955:CD36 Antigens; D051242:Caveolin 1; D002791:Cholesterol, Dietary; D013261:Sterols; D002784:Cholesterol