Group V secretory phospholipase A2 plays a pathogenic role in myocardial ischaemia-reperfusion injury.

Abstract

AIMS:

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.

METHODS AND 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.

CONCLUSION:

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: Toshiaki Yano, Daisuke Fujioka, Yukio Saito, Tsuyoshi Kobayashi, Takamitsu Nakamura, Jun-ei Obata, Kenichi Kawabata, Kazuhiro Watanabe, Yosuke Watanabe, Hideto Mishina, Shun Tamaru, Kiyotaka Kugiyama
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 90 Issue 2 Pg. 335-43 (May 01 2011) ISSN: 1755-3245 [Electronic] England
• PMID: 21169294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Leukotriene B4
• Arachidonic Acid
• Thromboxane B2
• Group IV Phospholipases A2
• Group V Phospholipases A2
• Casp3 protein, mouse
• Casp8 protein, mouse
• Caspase 3
• Caspase 8

Topics

• Animals
• Arachidonic Acid (metabolism)
• Caspase 3 (metabolism)
• Caspase 8 (metabolism)
• Cells, Cultured
• Echocardiography
• Enzyme Inhibitors (pharmacology)
• Group IV Phospholipases A2 (metabolism)
• Group V Phospholipases A2 (antagonists & inhibitors, genetics, metabolism)
• In Situ Nick-End Labeling
• Leukotriene B4 (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardial Infarction (diagnostic imaging, metabolism, pathology)
• Myocardial Reperfusion Injury (diagnostic imaging, metabolism, pathology)
• Myocardium (enzymology, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Thromboxane B2 (metabolism)