Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion

Cardiovasc Res. 2010 Jan 1;85(1):155-66. doi: 10.1093/cvr/cvp275.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Animals
  • Apoptosis
  • Disease Models, Animal
  • Echocardiography
  • Fatty Acids / metabolism*
  • Inflammation / etiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Neutrophil Infiltration
  • Nitric Oxide / metabolism*
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Thiocarbamates / pharmacology
  • Transcription Factor RelA / metabolism


  • Fatty Acids
  • Thiocarbamates
  • Transcription Factor RelA
  • prolinedithiocarbamate
  • Nitric Oxide
  • Proline