title: Cytosolic phospholipase A(2)α protects against ischemia/reperfusion injury in the heart.
abstract: 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).
authors: Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Risto.Kerkela@oulu.fi
authors: Risto
authors: R
authors: Kerkelä
authors: Matthieu
authors: M
authors: Boucher
authors: Raihana
authors: R
authors: Zaka
authors: Erhe
authors: E
authors: Gao
authors: David
authors: D
authors: Harris
authors: Jarkko
authors: J
authors: Piuhola
authors: Jianliang
authors: J
authors: Song
authors: Raisa
authors: R
authors: Serpi
authors: Kathleen C
authors: KC
authors: Woulfe
authors: Joseph Y
authors: JY
authors: Cheung
authors: Eileen
authors: E
authors: O'Leary
authors: Joseph V
authors: JV
authors: Bonventre
authors: Thomas
authors: T
authors: Force
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002469:Cell Separation; D003243:Consciousness; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054513:Group IV Phospholipases A2 / Q000172:deficiency / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016595:Misoprostol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000201:enzymology* / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D012307:Risk Factors; D015398:Signal Transduction / Q000187:drug effects; D013686:Telemetry
chemical_list: D016595:Misoprostol; D048049:Extracellular Signal-Regulated MAP Kinases; D054513:Group IV Phospholipases A2; D015232:Dinoprostone