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World J Gastroenterol. Dec 21, 2010; 16(47): 5946-5952
Published online Dec 21, 2010. doi: 10.3748/wjg.v16.i47.5946
A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport
Ryan E Temel, J Mark Brown
Ryan E Temel, J Mark Brown, Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, United States
Author contributions: Temel RE and Brown JM contributed equally to this paper.
Supported by Pathway to Independence Grants (5R00HL088528 to Temel RE and 1K99-HL096166 to Brown JM) from the National Heart, Lung, and Blood Institute
Correspondence to: Ryan E Temel, PhD, Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, United States. rtemel@wfubmc.edu
Telephone: +1-336-7131163 Fax: +1-336-7166279
Received: July 2, 2010
Revised: August 2, 2010
Accepted: August 9, 2010
Published online: December 21, 2010
Abstract

Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-mediated delivery of peripheral cholesterol to the liver for biliary excretion out of the body. However, recent studies have revealed a novel pathway for RCT that does not rely on biliary secretion. This non-biliary pathway rather involves the direct excretion of cholesterol by the proximal small intestine. Compared to RCT therapies that augment biliary sterol loss, modulation of non-biliary fecal sterol loss through the intestine is a much more attractive therapeutic strategy, given that excessive biliary cholesterol secretion can promote gallstone formation. However, we are at an early stage in understanding the molecular mechanisms regulating the non-biliary pathway for RCT, and much additional work is required in order to effectively target this pathway for CHD prevention. The purpose of this review is to discuss our current understanding of biliary and non-biliary contributions to RCT with particular emphasis on the possibility of targeting the intestine as an inducible cholesterol secretory organ.

Keywords: Cholesterol; Intestine; Bile; Lipoprotein; Reverse cholesterol transport