Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury
Standard
Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury. / Cole, Marsha P; Rudolph, Tanja K; Khoo, Nicholas K H; Motanya, Uche N; Golin-Bisello, Franca; Wertz, Jeffrey W; Schopfer, Francisco J; Rudolph, Volker; Woodcock, Steven R; Bolisetty, Subhashini; Ali, Muhammad S; Zhang, Jifeng; Chen, Y Eugene; Agarwal, Anupam; Freeman, Bruce A; Bauer, Philip M.
in: CIRC RES, Jahrgang 105, Nr. 10, 06.11.2009, S. 965-972.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury
AU - Cole, Marsha P
AU - Rudolph, Tanja K
AU - Khoo, Nicholas K H
AU - Motanya, Uche N
AU - Golin-Bisello, Franca
AU - Wertz, Jeffrey W
AU - Schopfer, Francisco J
AU - Rudolph, Volker
AU - Woodcock, Steven R
AU - Bolisetty, Subhashini
AU - Ali, Muhammad S
AU - Zhang, Jifeng
AU - Chen, Y Eugene
AU - Agarwal, Anupam
AU - Freeman, Bruce A
AU - Bauer, Philip M
PY - 2009/11/6
Y1 - 2009/11/6
N2 - 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.
AB - 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.
KW - Animals
KW - Cell Movement/drug effects
KW - Femoral Artery/enzymology
KW - Gene Expression Regulation, Enzymologic/drug effects
KW - Heme Oxygenase (Decyclizing)/biosynthesis
KW - Inflammation/metabolism
KW - Mice
KW - Mice, Knockout
KW - Nitric Oxide/metabolism
KW - Nitro Compounds/metabolism
KW - Oleic Acids/metabolism
KW - Oxidation-Reduction/drug effects
KW - Platelet-Derived Growth Factor/pharmacology
KW - Rats
KW - Tunica Intima/enzymology
KW - Up-Regulation/drug effects
U2 - 10.1161/CIRCRESAHA.109.199075
DO - 10.1161/CIRCRESAHA.109.199075
M3 - SCORING: Journal article
C2 - 19797175
VL - 105
SP - 965
EP - 972
JO - CIRC RES
JF - CIRC RES
SN - 0009-7330
IS - 10
ER -