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P46:Low sodium nitrite (but not nitrate) concentrations attenuate MMP-9 production by endothelial cells

Authors
Journal
Nitric Oxide
1089-8603
Publisher
Elsevier
Publication Date
Volume
31
Identifiers
DOI: 10.1016/j.niox.2013.02.048
Disciplines
  • Biology
  • Medicine

Abstract

Reduced nitric oxide (NO) bioavailability and imbalanced matrix metalloproteinase (MMP) activity have important roles in the pathogenesis of cardiovascular diseases, and some NO donors were shown to downregulate MMP expression in some cell types. However, while nitrite and nitrate can be recycled back to NO by non enzymatic and enzymatic mechanisms as an alternative to NO formation from l-arginine, no previous study has examined whether sodium nitrite can downregulate stimulated MMP release by endothelial cells. Objective We examined the effect of sodium nitrite and sodium nitrate on MMP-9 production by endothelial cells. Methods Human umbilical vein endothelial cells were cultured in a modified DMEM (iron(III) nitrate is replaced by iron(III) sulfate) and treated for 24h with 10nM phorbol myristate acetate (PMA; a MMP-9 inducer) and sodium nitrite or sodium nitrate, or their vehicles. Conditioned medium were analyzed by gelatin zimography to assess MMP-9 activity. Results PMA increased MMP-9 activity from 0.02±0.01 arbitrary units (AU) to 1.14±0.34AU (P<0.05). While low nitrite concentrations (0.2 or 2μM) attenuated the increases in MMP-9 activity induced by PMA (0.77±0.12AU or 0.71±0.14AU, respectively; both P<0.05 vs. PMA), high nitrite concentrations (10 or 20μM) had no effects on PMA-induced increases in MMP-9 activity (0.88±0.14AU or 1.18±0.36AU, respectively; both P>0.05 vs. PMA). Both low (10 or 100μM) or high (200 or 400μM) nitrate concentrations had no effects on PMA-induced increases in MMP-9 activity PMA (P>0.05 vs. PMA). Conclusion Our results suggest that low nitrite (but not nitrate) concentrations attenuate MMP-9 production by endothelial cells. Financial support FAPESP, CNPq, FAEPA. Disclosure Nothing to disclose.

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