title: Group V secretory phospholipase A2 plays a pathogenic role in myocardial ischaemia-reperfusion injury.
abstract: OBJECTIVE
  Group V secretory phospholipase A(2) (sPLA(2)-V) is highly expressed in the heart. This study examined (i) the role of sPLA(2)-V in myocardial ischaemia-reperfusion (I/R) injury and (ii) the cooperative action of sPLA(2)-V and cytosolic PLA(2) (cPLA(2)) in myocardial I/R injury, using sPLA(2)-V knockout (sPLA(2)V(-/-)) mice.
  
  
  RESULTS
  Myocardial I/R injury was created by 1 h ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. The sPLA(2)V(-/-) mice had a 44% decrease in myocardial infarct size, a preservation of echocardiographic LV function (%fractional shortening: 40 ± 3.5 vs. 21 ± 4.6, respectively), and lower content of leucotriene B(4) (LTB(4)) and thromboxane B(2) (TXB(2)) (40 and 37% lower, respectively) in the ischaemic myocardium after I/R compared with wild-type (WT) mice. Intraperitoneal administration of AACOCF3 or MAFP, inhibitors of cPLA(2) activity, decreased myocardial infarct size and myocardial content of LTB(4) and TXB(2) in both genotyped mice. The decrease in myocardial infarct size and content of LTB(4) and TXB(2) after cPLA(2) inhibitor administration was greater in WT mice than in sPLA(2)V(-/-) mice. I/R increased phosphorylation of extracellular signal-related kinase 1/2, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases in the ischaemic myocardium in association with cPLA(2) phosphorylation. The I/R-induced increase in the phosphorylation of p38 and cPLA(2) was less in sPLA(2)-V(-/-) mice than in WT mice. Pretreatment with the p38 inhibitor SB202190 suppressed an increase in cPLA(2) phosphorylation after I/R in WT mice.
  
  
  CONCLUSIONS
  sPLA(2)-V plays an important role in the pathogenesis of myocardial I/R injury partly in concert with the activation of cPLA(2).
authors.affiliation: Department of Internal Medicine II, Faculty of Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Yamanashi, Chuo 409-3898, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yano
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Jun-ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hideto
authors.initials: H
authors.lastname: Mishina
authors.forename: Shun
authors.initials: S
authors.lastname: Tamaru
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2 / Q000378:metabolism; D054505:Group V Phospholipases A2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007975:Leukotriene B4; D016718:Arachidonic Acid; D013929:Thromboxane B2; D054513:Group IV Phospholipases A2; D054505:Group V Phospholipases A2; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8