on April 17, 2008
Published online before print April 17, 2008, doi: 10.1161/ATVBAHA.108.165803
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Submitted on February 27, 2008
Accepted on April 7, 2008
Cholesterol Absorption From the Intestine Is a Major Determinant of Reverse Cholesterol Transport From Peripheral Tissue Macrophages
Ephraim Sehayek * and Stanley L. Hazen
From the Departments of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, Ohio.
* To whom correspondence should be addressed. E-mail: sehayee{at}ccf.org.
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.
Methods and Results—Treatment 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.
Key words: atherosclerosis • cholesterol absorption • cholesterol efflux • ezetimibe • macrophage • reverse cholesterol transport