Cholesterol absorption from the intestine is a major determinant of reverse cholesterol transport from peripheral tissue macrophages.
OBJECTIVE
We examined the effect of ezetimibe, a cholesterol absorption (CA) inhibitor, and genetic determinants of CA on reverse cholesterol transport (RCT) from subcutaneously injected macrophages using a new dual isotope label technique.


RESULTS
Treatment of C57BL/6J mice with ezetimibe decreased dietary CA by 86% and increased RCT from peripheral tissue macrophages (PTM) by 6-fold (P<0.0001). Moreover, congenic 14DKK mice with a modest 41% decrease in dietary CA displayed a 67% increase in RCT from PTM (P<0.007).


CONCLUSIONS
These findings indicate that pharmacological and genetic modifiers of cholesterol absorption are major determinants of reverse cholesterol transport from peripheral tissue macrophages.
Sehayek
Ephraim
E
Department of Cell Biology, Cleveland Clinic, Ohio 44195, USA. sehayee@ccf.org
Hazen
Stanley L
SL
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001384:Azetidines / Q000494:pharmacology*; D002460:Cell Line; D017690:Cell Transplantation; D002791:Cholesterol, Dietary / Q000097:blood / Q000378:metabolism*; D000069438:Ezetimibe; D005243:Feces / Q000737:chemistry; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects* / Q000235:genetics; D007422:Intestines / Q000187:drug effects*; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D012855:Sitosterols / Q000378:metabolism
D000924:Anticholesteremic Agents; D001384:Azetidines; D002791:Cholesterol, Dietary; D012855:Sitosterols; C021255:stigmastanol; D000069438:Ezetimibe