on June 17, 2004
Published online before print June 17, 2004, doi: 10.1161/01.ATV.0000135981.61827.9d
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Submitted on April 27, 2004
Accepted on June 4, 2004
Divergent Effects of the Catalytic and Bridging Functions of Hepatic Lipase on Atherosclerosis
Helén L. Dichek *;
From the Department of Pediatrics, University of Washington, Seattle, Wash.
* To whom correspondence should be addressed. E-mail: hdichek{at}u.washington.edu.
Objective--Increased expression of human hepatic lipase (HL) or a catalytically inactive (ci) HL clears plasma cholesterol in mice deficient in low-density lipoprotein receptors (LDLr) and murine HL. We hypothesized that increased expression of both HL and ciHL reduces atherosclerosis in these mice.
Methods and Results--Mice deficient in both LDLr and murine HL, alone or transgenically expressing similar levels of either human HL or ciHL, were fed a high-fat, cholesterol-enriched "Western" diet for 3 months to accelerate the development of atherosclerosis. Levels of plasma lipids, insulin, glucose, and liver enzymes were measured monthly, and aortic atherosclerosis was quantitated after 3 months. Plasma insulin, glucose, and liver enzyme levels did not differ significantly from controls. After 3 months, expression of HL reduced plasma cholesterol by 55% to 65% and reduced atherosclerosis by 40%. Surprisingly, expression of ciHL did not reduce plasma cholesterol or atherosclerosis.
Conclusions--High levels of HL, but not ciHL, delay the development of atherosclerosis in mice deficient in LDLr and mHL.
Key words: hepatic lipase • atherosclerosis • bridging function • fatty liver • mouse models
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