C-reactive protein enhances macrophage lipoprotein lipase expression.

Journal of Lipid Research
Fritz MaingretteGeneviève Renier

Abstract

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....Continue Reading

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Citations

Aug 5, 2010·Current Opinion in Lipidology·Gunilla Olivecrona, Thomas Olivecrona
Mar 3, 2011·Journal of Lipid Research·Xue Qiang ZhaoYun Zhang
Dec 3, 2014·Atherosclerosis·Yuan LiChao-Ke Tang
Apr 12, 2014·Biochimica Et Biophysica Acta·Sander Kersten
Jan 25, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Verónica MiksztowiczGabriela Berg

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