Resolvin E1 protects the rat heart against reperfusion injury

K. T. Keyes, Yumei Ye, Y. Lin, C. Zhang, J. R. Perez-Polo, P. Gjorstrup, Y. Birnbaum

Research output: Contribution to journalArticle

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Abstract

The purpose of the present study was to assess whether resolvin E1 (RvE1), an anti-inflammatory mediator derived from eicosapentaenoic acid, would limit myocardial infarct size in the rat. The H9c2 cell line was used to assess whether RvE1 has direct protective effects on cardiomyocytes. In in vivo experiments, Male Sprague-Dawley rats underwent 30 min of ischemia/4 h of reperfusion. Before reperfusion, rats received intravenous RvE1 (0, 0.03, 0.1, or 0.3mg/kg). In in vitro experiments, H9c2 cells were incubated with RvE1 (0, 1, 10, 100, or 1000 nM). Cells were subjected to 18 h of incubation under normoxic conditions, 16 h of hypoxia, or 16 h of hypoxia and 2 h of reoxygenation. In vivo, RvE1 dose dependently reduced infarct size (30.7 ± 1.7% of the area at risk in the control group and 29.1 ± 1.6%, 14.7 ± 1.3%, and 9.0 ± 0.6% in the 0.03, 0.1, and 0.3 mg/kg groups, respectively, P < 0.001). In vitro, RvE1 increased viability and decreased apoptosis in a dose-dependent fashion in cells exposed to hypoxia or hypoxia/reoxygenation. A maximal effect was achieved at a concentration of 100 nM. RvE1 augmented phosphoinositide 3-kinase activity, attenuated caspase-3 activity, and augmented calcium-dependent nitric oxide synthase activity in cells exposed to hypoxia or hypoxia/reoxygenation. RvE1 increased Akt, ERK1/2, and endothelial nitric oxide synthase phosphorylation and attenuated the levels of activated caspase-3 and phosphorylated p38 levels. AG-1478, an EGF receptor tyrosine kinase inhibitor, blocked the protective effect of RvE1 both in vivo and in vitro and attenuated the RvE1-induced increase in Akt and ERK1/2 phosphorylation. In conclusion, RvE1, an anti-inflammatory mediator derived from eicosapentaenoic acid, has a direct protective effect on cardiomyocytes against ischemia-reperfusion injury and limits infarct size when administered intravenously before reperfusion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

Reperfusion Injury
Reperfusion
Eicosapentaenoic Acid
Cardiac Myocytes
Caspase 3
5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid
Anti-Inflammatory Agents
Phosphorylation
1-Phosphatidylinositol 4-Kinase
Nitric Oxide Synthase Type III
Epidermal Growth Factor Receptor
Nitric Oxide Synthase
Protein-Tyrosine Kinases
Sprague Dawley Rats
Hypoxia
Ischemia
Myocardial Infarction
Apoptosis
Calcium
Cell Line

Keywords

  • Apoptosis
  • Epidermal growth factor receptor
  • Infarct size
  • Ischemia-reperfusion injury

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Resolvin E1 protects the rat heart against reperfusion injury. / Keyes, K. T.; Ye, Yumei; Lin, Y.; Zhang, C.; Perez-Polo, J. R.; Gjorstrup, P.; Birnbaum, Y.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 299, No. 1, 07.2010.

Research output: Contribution to journalArticle

Keyes, K. T. ; Ye, Yumei ; Lin, Y. ; Zhang, C. ; Perez-Polo, J. R. ; Gjorstrup, P. ; Birnbaum, Y. / Resolvin E1 protects the rat heart against reperfusion injury. In: American Journal of Physiology - Heart and Circulatory Physiology. 2010 ; Vol. 299, No. 1.
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AU - Gjorstrup, P.

AU - Birnbaum, Y.

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