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Early steps in reverse cholesterol transport: cholesteryl ester hydrolase and other hydrolases

Ghosh, Shobha

Current Opinion in Endocrinology, Diabetes & Obesity: April 2012 - Volume 19 - Issue 2 - p 136–141
doi: 10.1097/MED.0b013e3283507836
LIPIDS: Edited by Annabelle Rodriguez

Purpose of review: Several controversies exist related to the molecular identity and subcellular localization of the enzyme catalyzing macrophage cholesteryl ester hydrolysis. Some of these issues have been reviewed earlier and this review summarizes new developments that describe effects of overexpression or gene ablation. The main objective is to highlight the disagreement between lack of gene expression and incomplete abolition of macrophage cholesteryl ester hydrolytic activity and to emphasize the importance of redundancy.

Recent findings: New information resulting from the continuing characterization of the various cholesteryl ester hydrolases (hormone-sensitive lipase, HSL; cholesteryl ester hydrolase, CEH; and KIAA1363/NCEH1) is reviewed. Whereas CEH overexpression leads to beneficial effects such as decreased inflammation, improved glucose tolerance/insulin sensitivity, and attenuation of atherosclerotic lesion progression, deficiency/ablation of HSL or KIAA1363/NCEH1 results in incomplete loss of macrophage cholesteryl ester hydrolysis/turnover. New paradigms challenging the classical view of cytoplasmic cholesteryl ester hydrolysis and reverse cholesterol transport are also presented.

Summary: The observed beneficial effects of CEH overexpression identify macrophage cholesteryl ester hydrolysis as an important therapeutic target and future studies will determine whether similar effects are obtained with overexpression of HSL or KIAA1363/NCEH1. It is imperative that, for clinical benefit, mechanisms to enhance endogenous cholesteryl ester hydrolase(s) are established.

Division of Pulmonary and Critical Care, Department of Internal Medicine, VCU Medical Center, Richmond, Virginia, USA

Correspondence to Shobha Ghosh, PhD, Professor of Medicine and Physiology, Division of Pulmonary and Critical Care, Department of Internal Medicine, VCU Medical Center, Richmond, VA 23298-0050, USA. Tel: +1 804 827 1012; fax: +1 804 628 1204; e-mail: shobha@vcu.edu

© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins