Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury.

Academic Article

Abstract

  • RATIONALE: Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. OBJECTIVE: The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. METHODS AND RESULTS: The in vivo administration (21 days) of nitro-oleic acid (OA-NO(2)) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO(2) treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals,P<0.0001). Increased heme oxygenase (HO)-1 expression accounted for much of the vascular protection induced by OA-NO(2) in both cultured aortic smooth muscle cells and in vivo. Inhibition of HO by Sn(IV)-protoporphyrin or HO-1 small interfering RNA reversed OA-NO(2)-induced inhibition of platelet-derived growth factor-stimulated rat aortic smooth muscle cell migration. The upregulation of HO-1 expression also accounted for the antistenotic actions of OA-NO(2) in vivo, because inhibition of neointimal hyperplasia following femoral artery injury was abolished in HO-1(-/-) mice (OA-NO(2)-treated wild-type versus HO-1(-/-) mice, P=0.016). CONCLUSIONS: In summary, electrophilic nitro-fatty acids induce salutary gene expression and cell functional responses that are manifested by a clinically significant outcome, inhibition of neointimal hyperplasia induced by arterial injury.
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    Keywords

  • Animals, Cell Movement, Femoral Artery, Gene Expression Regulation, Enzymologic, Heme Oxygenase (Decyclizing), Inflammation, Mice, Mice, Knockout, Nitric Oxide, Nitro Compounds, Oleic Acids, Oxidation-Reduction, Platelet-Derived Growth Factor, Rats, Tunica Intima, Up-Regulation
  • Digital Object Identifier (doi)

    Authorlist

  • Cole MP; Rudolph TK; Khoo NKH; Motanya UN; Golin-Bisello F; Wertz JW; Schopfer FJ; Rudolph V; Woodcock SR; Bolisetty S
  • Start Page

  • 965
  • End Page

  • 972
  • Volume

  • 105
  • Issue

  • 10