In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 105, No. 10 ( 2009-11-06), p. 965-972
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.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.109.199075
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2009
detail.hit.zdb_id:
1467838-X
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