Abstract
Linoleic safflower seed oil reduces the development of diet‐induced atherosclerosis. However, the underlying mechanism of anti‐atherosclerotic effect remains unclear so far. The present study aims to investigate the effect of linoleic acid (LA) on PDGF‐induced migration of rat vascular smooth muscle cells (rSMC) and its molecular mechanism. Wound healing assay and transwell migration assay indicated that PDGF induced migration of rSMC relative to control. LA pretreatment reduced PDGF‐induced migration in a dose‐dependent manner. These results were consistent with that of DQ gelatin degradation. PDGF increased the phosphorylations of ERK and Akt. LA inhibited PDGF‐induced phosphorylation of Akt but not that of ERK. Moreover, LA significantly increased mRNA levels and protein expressions of tissue inhibitor of metalloproteinase (TIMP)‐1 and TIMP‐2. TIMP activity by reverse zymography was also increased by LA. We showed that TIMP‐1 induction by LA was regulated by JunB/AP‐1 as determined by ChIP analyses. The transfection of TIMP‐1 or TIMP2 siRNA reversed the inhibitory effect of LA on the PDGF induced migration. We conclude that LA effectively suppressed the PDGF‐induced rSMC migration via induction of TIMP1/2 suggesting that LA might potently prevent migration‐related disease such as restenosis and atherosclerosis.
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