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PLoS One. 2007 Nov 7;2(11):e1137.

PGC-1alpha inhibits oleic acid induced proliferation and migration of rat vascular smooth muscle cells.

Author information

1
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China.

Abstract

BACKGROUND:

Oleic acid (OA) stimulates vascular smooth muscle cell (VSMC) proliferation and migration. The precise mechanism is still unclear. We sought to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 alpha (PGC-1alpha) on OA-induced VSMC proliferation and migration.

PRINCIPAL FINDINGS:

Oleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1alpha in VSMCs. OA treatment resulted in a reduction of PGC-1alpha expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1alpha prevented OA-induced VSMC proliferation and migration while suppression of PGC-1alpha by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA) treatment led to opposite effects. This saturated fatty acid induced PGC-1alpha expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1alpha on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation.

CONCLUSIONS:

OA and PA regulate PGC-1alpha expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1alpha expression while PA reverses the effects of OA by inducing PGC-1alpha expression. Upregulation of PGC-1alpha in VSMCs provides a potential novel strategy in preventing atherosclerosis.

PMID:
17987121
PMCID:
PMC2043491
DOI:
10.1371/journal.pone.0001137
[Indexed for MEDLINE]
Free PMC Article
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