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

Aims Group V secretory phospholipase A2 (sPLA2-V) is highly expressed in the heart. This study examined (i) the role of sPLA2-V in myocardial ischaemia–reperfusion (I/R) injury and (ii) the cooperative action of sPLA2-V and cytosolic PLA2 (cPLA2) in myocardial I/R injury, using sPLA2-V knockout (sPLA2V−/−) 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 sPLA2V−/− 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 B4 (LTB4) and thromboxane B2 (TXB2) (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 cPLA2 activity, decreased myocardial infarct size and myocardial content of LTB4 and TXB2 in both genotyped mice. The decrease in myocardial infarct size and content of LTB4 and TXB2 after cPLA2 inhibitor administration was greater in WT mice than in sPLA2V−/− 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 cPLA2 phosphorylation. The I/R-induced increase in the phosphorylation of p38 and cPLA2 was less in sPLA2-V−/− mice than in WT mice. Pretreatment with the p38 inhibitor SB202190 suppressed an increase in cPLA2 phosphorylation after I/R in WT mice. Conclusion sPLA2-V plays an important role in the pathogenesis of myocardial I/R injury partly in concert with the activation of cPLA2.