Open AccessCytosolic Phospholipase A 2 α Protects against Ischemia/Reperfusion Injury in the Heart
Author(s) -
Kerkelä Risto,
Boucher Matthieu,
Zaka Raihana,
Gao Erhe,
Harris David,
Piuhola Jarkko,
Song Jianliang,
Serpi Raisa,
Woulfe Kathleen C.,
Cheung Joseph Y.,
O’Leary Eileen,
Bonventre Joseph V.,
Force Thomas
Publication year - 2011
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2011.00294.x
Subject(s) - ischemia , medicine , phospholipase a2 , in vivo , pharmacology , phospholipase a , pathophysiology , reperfusion injury , stroke (engine) , prostaglandin e , phospholipase , cardiology , biology , biochemistry , enzyme , mechanical engineering , microbiology and biotechnology , engineering
Studies with sPLA 2 Group X, and cPLA 2 α gene‐targeted mice suggest that absence of sPLA 2 Group X results in protection from ischemia/reperfusion (I/R) injury in the heart, and absence of cPLA 2 α Group IV is protective in the brain. Although latter studies might suggest a similar deleterious role for cPLA 2 α in I/R injury in the heart, the pathophysiology of stroke is intricately related to excitotoxicity and cannot necessarily be extrapolated to the heart. We report here that unlike findings in the brain, cPLA 2 α (−/−) mice have exaggerated injury following I/R in vivo . In contrast, there is no difference in injury induced by simulated ischemia in cardiomyocytes isolated from cPLA 2 α (−/−) versus cPLA 2 α (+/+) mice. This suggests that cPLA 2 α does not have an important cardiomyocyte autonomous effect on ischemic injury. Prostaglandin E 2 (PGE 2 ) levels are significantly reduced in the hearts of the cPLA 2 α (−/−) mice, and the enhanced injury is ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that cPLA 2 α is cardioprotective in vivo , and this is likely via cPLA 2 α‐mediated production of cardioprotective eicosanoids. These studies are the first to identify a protective role for cPLA 2 in I/R injury in any organ and raise concerns over long‐term inhibition of cPLA 2 . Clin Trans Sci 2011; Volume 4: 236–242