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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1296.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Cholesterol Absorption From the Intestine Is a Major Determinant of Reverse Cholesterol Transport From Peripheral Tissue Macrophages

Ephraim Sehayek; Stanley L. Hazen

From the Departments of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, Ohio.

Correspondence to Ephraim Sehayek, MD, 9500 Euclid Ave, NE-10 Cleveland, OH 44195. 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 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.

Key Words: atherosclerosis • cholesterol absorption • cholesterol efflux • ezetimibe • macrophage • reverse cholesterol transport

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