17β-Estradiol inhibits oleic acid-induced rat VSMC Proliferation and migration by restoring PGC-1α expression

Estrogen shows a vasoprotective role through inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs). The mechanism underlying the effect of estrogen, however, is not completely understood. Here, we explored the role of peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1alpha (PGC-1α) in estrogen-mediated vasoprotection. Firstly, we showed that oleic acid (OA) decreased PGC-1α expression while stimulating VSMC proliferation and migration. In contrast, administration of VSMCs with 17β-estradiol (E2, 1 or 10 nM) significantly restored OA-decreased PGC-1α expression, treatment with 10 nM E2 almost completely abolished OA-induced VSMC proliferation and migration. Secondly, by using PGC-1α siRNA, the inhibitory effect of E2 on VSMC growth is strongly reduced via suppressing PGC-1α expression, indicating that E2 may exert its role through restoring PGC-1α. Finally, E2 (10 nM) treatment inhibits OA-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, however, suppression of PGC-1α expression abolishes this inhibitory effect of E2. Our findings demonstrate for the first time that in OA-stimulated rat VSMCs, treatment with E2 (1 or 10 nM) diminishes VSMC proliferation and migration via restoring OA-decreased PGC-1α expression. This observation offers a novel molecular basis of the vasoprotective effect of estrogen.