Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion
Standard
Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion. / Rudolph, Volker; Rudolph, Tanja K; Schopfer, Francisco J; Bonacci, Gustavo; Woodcock, Steven R; Cole, Marsha P; Baker, Paul R S; Ramani, Ravi; Freeman, Bruce A.
in: CARDIOVASC RES, Jahrgang 85, Nr. 1, 01.01.2010, S. 155-166.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion
AU - Rudolph, Volker
AU - Rudolph, Tanja K
AU - Schopfer, Francisco J
AU - Bonacci, Gustavo
AU - Woodcock, Steven R
AU - Cole, Marsha P
AU - Baker, Paul R S
AU - Ramani, Ravi
AU - Freeman, Bruce A
PY - 2010/1/1
Y1 - 2010/1/1
N2 - AIMS: Nitrated fatty acids (NO(2)-FA) have been identified as endogenous anti-inflammatory signalling mediators generated by oxidative inflammatory reactions. Herein the in vivo generation of nitro-oleic acid (OA-NO(2)) and nitro-linoleic acid (LNO(2)) was measured in a murine model of myocardial ischaemia and reperfusion (I/R) and the effect of exogenous administration of OA-NO(2) on I/R injury was evaluated.METHODS AND RESULTS: In C57/BL6 mice subjected to 30 min of coronary artery ligation, endogenous OA-NO(2) and LNO(2) formation was observed after 30 min of reperfusion, whereas no NO(2)-FA were detected in sham-operated mice and mice with myocardial infarction without reperfusion. Exogenous administration of 20 nmol/g body weight OA-NO(2) during the ischaemic episode induced profound protection against I/R injury with a 46% reduction in infarct size (normalized to area at risk) and a marked preservation of left ventricular function as assessed by transthoracic echocardiography, compared with vehicle-treated mice. Administration of OA-NO(2) inhibited activation of the p65 subunit of nuclear factor kappaB (NFkappaB) in I/R tissue. Experiments using the NFkappaB inhibitor pyrrolidinedithiocarbamate also support that protection lent by OA-NO(2) was in part mediated by inhibition of NFkappaB. OA-NO(2) inhibition of NFkappaB activation was accompanied by suppression of downstream intercellular adhesion molecule 1 and monocyte chemotactic protein 1 expression, neutrophil infiltration, and myocyte apoptosis.CONCLUSION: This study reveals the de novo generation of fatty acid nitration products in vivo and reveals the anti-inflammatory and potential therapeutic actions of OA-NO(2) in myocardial I/R injury.
AB - AIMS: Nitrated fatty acids (NO(2)-FA) have been identified as endogenous anti-inflammatory signalling mediators generated by oxidative inflammatory reactions. Herein the in vivo generation of nitro-oleic acid (OA-NO(2)) and nitro-linoleic acid (LNO(2)) was measured in a murine model of myocardial ischaemia and reperfusion (I/R) and the effect of exogenous administration of OA-NO(2) on I/R injury was evaluated.METHODS AND RESULTS: In C57/BL6 mice subjected to 30 min of coronary artery ligation, endogenous OA-NO(2) and LNO(2) formation was observed after 30 min of reperfusion, whereas no NO(2)-FA were detected in sham-operated mice and mice with myocardial infarction without reperfusion. Exogenous administration of 20 nmol/g body weight OA-NO(2) during the ischaemic episode induced profound protection against I/R injury with a 46% reduction in infarct size (normalized to area at risk) and a marked preservation of left ventricular function as assessed by transthoracic echocardiography, compared with vehicle-treated mice. Administration of OA-NO(2) inhibited activation of the p65 subunit of nuclear factor kappaB (NFkappaB) in I/R tissue. Experiments using the NFkappaB inhibitor pyrrolidinedithiocarbamate also support that protection lent by OA-NO(2) was in part mediated by inhibition of NFkappaB. OA-NO(2) inhibition of NFkappaB activation was accompanied by suppression of downstream intercellular adhesion molecule 1 and monocyte chemotactic protein 1 expression, neutrophil infiltration, and myocyte apoptosis.CONCLUSION: This study reveals the de novo generation of fatty acid nitration products in vivo and reveals the anti-inflammatory and potential therapeutic actions of OA-NO(2) in myocardial I/R injury.
KW - Alkylation
KW - Animals
KW - Apoptosis
KW - Disease Models, Animal
KW - Echocardiography
KW - Fatty Acids/metabolism
KW - Inflammation/etiology
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Myocardial Ischemia/metabolism
KW - Myocardial Reperfusion Injury/prevention & control
KW - Neutrophil Infiltration
KW - Nitric Oxide/metabolism
KW - Proline/analogs & derivatives
KW - Thiocarbamates/pharmacology
KW - Transcription Factor RelA/metabolism
U2 - 10.1093/cvr/cvp275
DO - 10.1093/cvr/cvp275
M3 - SCORING: Journal article
C2 - 19666678
VL - 85
SP - 155
EP - 166
JO - CARDIOVASC RES
JF - CARDIOVASC RES
SN - 0008-6363
IS - 1
ER -