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

Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):197-203. doi: 10.1161/01.ATV.0000249683.80414.d9. Epub 2006 Oct 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Carotid Arteries / metabolism*
  • Carotid Arteries / pathology
  • Cell Adhesion / genetics
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Female
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / pathology
  • Hypertriglyceridemia / genetics
  • Hypertriglyceridemia / metabolism
  • Hypertriglyceridemia / pathology
  • Lipid Metabolism / genetics
  • Lipid Metabolism / physiology*
  • Lipoprotein Lipase / genetics
  • Lipoprotein Lipase / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Monocytes / cytology
  • Up-Regulation / genetics
  • Up-Regulation / physiology*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Apolipoproteins E
  • Vascular Cell Adhesion Molecule-1
  • Lipoprotein Lipase