Yingzi Chang
Hyperinsulinemia is associated with an increased risk of vascular restenosis after angioplasty. As a major proinflammatory cytokine, interleukin-6 (IL-6) induces motogenic effects on vascular smooth muscle cells. Attenuation of vascular injury-induced neointima thickening was observed by blocking STAT3 tyrosine phosphorylation, which is a key component of IL-6 signaling. A non-receptor protein tyrosine phosphatase, PTP1B, plays a counter-regulatory role in injury-induced neointima formation by inhibiting platelet-derived growth factor (PDGF)-induced smooth muscle cell migration and proliferation. However, the role of IL-6, in association with hyperinsulinemia, with an increased risk of vascular restenosis and the involvement of PTP1B in this process has never been studied. Using subcultured (passages 5-9) smooth muscle cells isolated from rat aortae, we found that: 1) chronic insulin treatment potentiated IL-6-induced smooth muscle cell migration and STAT3 tyrosine phosphorylation; 2) chronic insulin dose-dependently suppressed the baseline expression of endogenous PTP1B; 3) overexpressing wild-type PTP1B significantly attenuated whereas C215S-PTP1B enhanced IL-6-induced STAT3 phosphorylation and smooth muscle cell migration. The aforementioned results suggest that inhibition of baseline expression of PTP1B and subsequent potentiation of IL-6-stimulated vascular smooth muscle migration may serve as a potential mechanism for increased risk of vascular restenosis after angioplasty in patients with insulin resistance.
