Group V secretory phospholipase A2 plays a pathogenic role in myocardial ischaemia-reperfusion injury.
Group V secretory phospholipase A2 plays a pathogenic role in myocardial ischaemia-reperfusion injury.
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DOI：
10.1093/cvr/cvq399
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发表时间：
2011-05
影响因子：
10.8
通讯作者：
T. Yano;Daisuke Fujioka;Yukio Saito;Tsuyoshi Kobayashi;Takamitsu Nakamura;J. Obata;K. Kawabata;Kazuhiro Watanabe;Yosuke Watanabe;Hideto Mishina;Shun Tamaru;K. Kugiyama
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文献类型：
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作者：
T. Yano;Daisuke Fujioka;Yukio Saito;Tsuyoshi Kobayashi;Takamitsu Nakamura;J. Obata;K. Kawabata;Kazuhiro Watanabe;Yosuke Watanabe;Hideto Mishina;Shun Tamaru;K. Kugiyama
AIMS V 组分泌性磷脂酶 A(2) (sPLA(2)-V) 在心脏中高度表达。本研究使用 sPLA(2)-V 敲除 (sPLA(2)V(-/-)) 小鼠，研究了 (i) sPLA(2)-V 在心肌缺血再灌注 (I/R) 损伤中的作用，以及 (ii) sPLA(2)-V 和胞质 PLA(2) (cPLA(2)) 在心肌 I/R 损伤中的协同作用。方法和结果 通过结扎左冠状动脉前降支 1 小时，然后再灌注 24 小时，造成心肌 I/R 损伤。 sPLA(2)V(-/-) 小鼠的心肌梗死面积减少了 44%，超声心动图 LV 功能得到保留（缩短分数：分别为 40 ± 3.5 与 21 ± 4.6），并且白三烯 B(4) (LTB(4)) 和血栓素 B(2) (TXB(2)) 含量较低（分别降低 40% 和 37%）。与野生型 (WT) 小鼠相比，I/R 后缺血性心肌。腹腔内给予AACOCF3或MAFP、cPLA(2)活性抑制剂，可减少两只基因型小鼠的心肌梗塞面积以及心肌中LTB(4)和TXB(2)的含量。与sPLA(2)V(-/-)小鼠相比，WT小鼠在给予cPLA(2)抑制剂后心肌梗塞面积以及LTB(4)和TXB(2)含量的减少更大。 I/R 增加了缺血心肌中与 cPLA(2) 磷酸化相关的细胞外信号相关激酶 1/2、c-Jun N 末端激酶和 p38 丝裂原激活蛋白激酶的磷酸化。 sPLA(2)-V(-/-) 小鼠中 I/R 诱导的 p38 和 cPLA(2) 磷酸化增加少于 WT 小鼠。 p38 抑制剂 SB202190 预处理可抑制 WT 小鼠 I/R 后 cPLA(2) 磷酸化的增加。结论 sPLA(2)-V在心肌I/R损伤的发病机制中发挥着重要作用，部分与cPLA(2)的激活相一致。
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).