on October 12, 2006
Published online before print October 12, 2006, doi: 10.1161/01.ATV.0000249683.80414.d9
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Submitted on June 5, 2006
Accepted on September 29, 2006
Expression of LPL in Endothelial-Intact Artery Results in Lipid Deposition and Vascular Cell Adhesion Molecule-1 Upregulation in Both LPL and ApoE-Deficient Mice
Jinyu Wang ;
From the Institute of Cardiovascular Sciences and Key Laboratory of Molecular Cardiovascular Sciences (J.W., X.X., W.H., L.C., G.L.), Ministry of Education, and the Department of Physiology and Pathophysiology (J.W., L.W., Y.Z.), Peking University Health Science Center, Beijing, China; the Cardiovascular Disease Laboratory (J.F.), Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Japan; and the Department of Medical Genetics (C.R., M.R.H.), University of British Columbia, Centre for Molecular Medicine and Therapeutics, Vancouver, Canada.
* To whom correspondence should be addressed. E-mail: vangeorgeliu{at}gmail.com.
Objective--Overexpression of lipoprotein lipase (LPL) in deendothelialized artery led to profound localized lipid deposition. In this study the role of LPL in atherogenesis in endothelial-intact carotid arteries was assessed in genetically hyperlipidemic LPL- and ApoE-deficient mice.
Methods and Results--Human wild-type LPL (hLPLwt), catalytically inactive LPL (hLPL194), or control alkaline phosphatase (hAP) were expressed in endothelial-intact carotid arteries via adenoviral vectors. Compared with Ad-hAP, lipid deposition in the arterial wall increased 10.0- and 5.1-fold for Ad-hLPLwt and Ad-hLPL194 in LPL-deficient mice, and 10.6- and 6.2-fold in ApoE-deficient mice, respectively. Vascular cell adhesion molecule-1 (VCAM-1) was upregulated in Ad-hLPLwt and Ad-hLPL194 transferred arteries.
Conclusions--Endothelial cell associated LPL, either active or inactive, in the arterial wall is a strong proatherosclerotic factor in both LPL- and ApoE-deficient mice.
Key words: lipoprotein lipase • atherosclerosis • vascular cell adhesion molecule-1 • mice • gene transfer
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