Key result
Nitric oxide inhibits IL-1β-stimulated MMP-9 induction in VSMCs by attenuating superoxide generation and ERK activation.
p-value: p=<0.05
Nitric oxide inhibits MMP-9 induction in vascular smooth muscle cells by attenuating superoxide generation and ERK activation, providing mechanistic insight into neointima formation after angioplasty.
Extends mechanistic insight into NO-mediated vascular remodeling; leaves open translation to clinical restenosis prevention.
Vascular smooth muscle (VSM) cell migration is a critical step in the development of a neointima after angioplasty. Matrix metalloproteinases (MMPs) degrade the basement membrane and extracellular matrix, facilitating VSM cell migration. Recently, we demonstrated that nitric oxide (NO) inhibits interleukin-1 beta (IL-1 beta)-stimulated MMP-9 induction in rat aortic VSM cells. In this study, we examined the hypothesis that NO inhibits MMP-9 induction by attenuating superoxide generation and extracellular signal-regulated kinase (ERK) activation. Stimulation of VSM cells with IL-1 beta significantly (P < 0.05) increased superoxide production, ERK activation, and MMP-9 induction. Pretreatment of VSM cells with the NO donor DETA NONOate significantly (P < 0.05) decreased IL-1 beta-stimulated superoxide generation. In addition, pretreatment of VSM cells with a specific ERK pathway inhibitor, PD-98059, or DETA NONOate inhibited IL-1 beta-stimulated ERK activation and MMP-9 induction. Direct exposure of VSM cells to increased superoxide levels by treatment with xanthine/xanthine oxidase increased ERK activation and MMP-9 induction, whereas pretreatment of cells with PD-98059 significantly (P < 0.05) inhibited xanthine/xanthine oxidase-stimulated ERK activation and MMP-9 induction. We conclude that NO inhibits IL-1 beta-stimulated MMP-9 induction by inhibiting superoxide generation and subsequent ERK activation.
No takes yet. Share an insight, caveat, or question.
Gurjar et al. (2001) studied Neointima development after angioplasty. Nitric oxide (NO donor DETA NONOate) vs. IL-1 beta stimulation alone was evaluated on MMP-9 induction, superoxide generation, and ERK activation (p=<0.05). Nitric oxide inhibits IL-1 beta-stimulated MMP-9 induction in vascular smooth muscle cells by attenuating superoxide generation and subsequent ERK activation (P<0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: