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Journal of Lipid Research, Vol. 49, 1926-1935, September 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

C-reactive protein enhances macrophage lipoprotein lipase expression

Fritz Maingrette*, Ling Li{dagger} and Geneviève Renier1,*,{dagger}

* Department of Nutrition, University of Montreal, Montreal, Quebec, Canada
{dagger} Department of Medicine, Centre Hospitalier de l'Université de Montréal Research Centre, Notre Dame Hospital, Montreal, Quebec, Canada

Published, JLR Papers in Press, 14 May 2008.

This study was supported by Diabète Québec.

1 To whom correspondence should be addressed. e-mail: genevieve.renier{at}umontreal.ca

High serum levels of C-reactive protein (CRP), a strong predictor of cardiovascular events, are documented in patients with type 2 diabetes. Accumulating evidence suggests that CRP could directly promote arterial damage. To determine the role of CRP in diabetic atherosclerosis, we examined the effect of CRP on the expression of macrophage lipoprotein lipase (LPL), a proatherogenic molecule upregulated in type 2 diabetes. Treatment of human macrophages with native CRP increased, in a dose- and time-dependent manner, LPL protein expression and secretion. Modified CRP reproduced these effects. Preincubation of human macrophages with antioxidants, protein kinase C (PKC), and mitogen-activated protein kinase (MAPK) inhibitors prevented CRP-induced LPL expression. Exposure of human macrophages to CRP further increased intracellular reactive oxygen species generation, classic PKC isozymes expression, and extracellular signal-regulated protein kinase 1/2 phosphorylation. In CRP-treated J774 macrophages, increased macrophage LPL mRNA levels and enhanced binding of nuclear proteins to the activated protein-1 (AP-1)-enhancing element were observed. These effects were prevented by antioxidants, as well as by PKC, MAPK, and AP-1 inhibitors. These data show for the first time that CRP directly increases macrophage LPL expression and secretion. Given the predominant role of macrophage LPL in atherogenesis, LPL might represent a novel factor underlying the adverse effect of CRP on the diabetic vasculature.

Supplementary key words atherosclerosis • type 2 diabetes • inflammation • oxidative stress • kinases


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