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


RESULTS
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.
Zhang
Yan
Y
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People's Republic of China.
Liu
Chang
C
Zhu
Lingyun
L
Jiang
Xiaohong
X
Chen
Xi
X
Qi
Xiaoqiang
X
Liang
Xiangying
X
Jin
Sonia
S
Zhang
Peixiang
P
Li
Qingguo
Q
Wang
Dongjin
D
Liu
Xiaofeng
X
Zeng
Ke
K
Zhang
Junfeng
J
Xiang
Yang
Y
Zhang
Chen-Yu
CY
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D019301:Oleic Acid / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000502:physiology*; D051381:Rats; D014157:Transcription Factors / Q000502:physiology*
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019301:Oleic Acid; D048049:Extracellular Signal-Regulated MAP Kinases