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Originally published In Press as doi:10.1194/jlr.M400069-JLR200 on June 8, 2004 Originally published In Press as doi:10.1194/jlr.M400069-JLR200 on June 1, 2004

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Journal of Lipid Research, Vol. 45, 1614-1623, September 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Endothelial lipase is synthesized by hepatic and aorta endothelial cells and its expression is altered in apoE-deficient mice

Kenneth C-W. Yu*, Christopher David{dagger}, Sujata Kadambi{dagger}, Andreas Stahl*,{dagger}, Ken-Ichi Hirata1,*, Tatsuro Ishida1,*, Thomas Quertermous*, Allen D. Cooper*,{dagger} and Sungshin Y. Choi2,{dagger}

* School of Medicine, Stanford University, Palo Alto, CA
{dagger} Research Institute, Palo Alto Medical Foundation, Palo Alto, CA

2 To whom correspondence should be addressed. e-mail: chois{at}pamfri.org

Both LPL and HL are synthesized in parenchymal cells, are secreted, and bind to endothelial cells. To learn where endothelial lipase (EL) is synthesized in adult animals, the localization of EL in mouse and rat liver was studied by immunohistochemical analysis. Furthermore, to test whether EL could play a role in atherogenesis, the expression of EL in the aorta and liver of apolipoprotein E knockout (EKO) mice was determined. EL in both mouse and rat liver was colocalized with vascular endothelial cells but not with hepatocytes. In contrast, HL was present in both hepatocytes and endothelial cells. By in situ hybridization, EL mRNA was present only in endothelial cells in liver sections. EL was also present at low levels in aorta of normal mice. We fed EKO mice and wild-type mice a variety of diets and determined EL expression in liver and aorta. EKO mice showed significant expression of EL in aorta. EL expression was lower in the liver of EKO mice than in normal mice. Cholesterol feeding decreased EL in liver of both types of mice. In the aorta, EL was higher in EKO than in wild-type mice, and cholesterol feeding had no effect.

Together, these data suggest that EL may be upregulated at the site of atherosclerotic lesions and thus could supply lipids to the area.

Abbreviations: apoA-I, apolipoprotein A-I; CA, cholic acid; DAPI, 4,6-diamidino-2-phenylindole; EKO, apolipoprotein E knockout; EL, endothelial lipase; HF, high-fat; IL-1ß, interleukin-1ß; NC, normal chow; NC+Chol, normal chow plus 2% cholesterol; TNF-{alpha}, tumor necrosis factor-{alpha}; vWF, von Willbrand factor

Supplementary key words apolipoprotein E • atherosclerosis • hepatic lipase • high-fat diet • lipoprotein lipase • real-time PCR


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