Abstract
BackgroundOleic 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 (PPARγ) coactivator-1 alpha (PGC-1α) on OA-induced VSMC proliferation and migration.Principal FindingsOleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1α in VSMCs. OA treatment resulted in a reduction of PGC-1α expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1α prevented OA-induced VSMC proliferation and migration while suppression of PGC-1α by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA) treatment led to opposite effects. This saturated fatty acid induced PGC-1α expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1α on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation.ConclusionsOA and PA regulate PGC-1α expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1α expression while PA reverses the effects of OA by inducing PGC-1α expression. Upregulation of PGC-1α in VSMCs provides a potential novel strategy in preventing atherosclerosis.
Highlights
Pathogenic development of atherosclerosis involves a complex series of events [1], of which abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) contribute significantly to the progression of atherosclerosis [2]
We found that Oleic acid (OA) and palmitic acid (PA) had an opposite role in regulating PGC-1a expression in rat VSMCs and PGC-1a inhibited OA-induced VSMC proliferation and migration via the inhibition of extracellular signal-regulated kinase (ERK) phosphorylation
It has reported that various saturated, unsaturated, and trans fatty acids, including monounsaturated and polyunsaturated, saturated fatty acids of varying chain length (C10:0 to C18:0), and trans fatty acids such as elaidic acid and trans-vaccenic acid which are abundantly present in hydrogenated vegetable oil and dairy products, had no effect on the expression of PGC-1a, except stearic acid (C18:0), induced PGC-1a mRNA 2.2fold in primary hepatocytes [28]
Summary
Pathogenic development of atherosclerosis involves a complex series of events [1], of which abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) contribute significantly to the progression of atherosclerosis [2]. OA, the most abundant unsaturated fatty acid in plasma [8], induces VSMC proliferation and migration by direct induction of extracellular signal-regulated kinase (ERK)-dependent mitogenic response [6,9,10,11]. Recent studies demonstrated that thiazolidinediones (TZDs), the ligands for nuclear receptor peroxisome proliferator-activated receptor gamma (PPARc), improved cardiovascular risk factors via exerting direct effects on vascular cells, for example, inhibition of VSMC proliferation and migration [12,13]. Oleic acid (OA) stimulates vascular smooth muscle cell (VSMC) proliferation and migration. Palmitic acid (PA) treatment led to opposite effects This saturated fatty acid induced PGC-1a expression and prevented OAinduced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1a on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation. Upregulation of PGC-1a in VSMCs provides a potential novel strategy in preventing atherosclerosis
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