Redistribution and abnormal activity of phospholipase A(2) isoenzymes in postinfarct congestive heart failure.
Redistribution and abnormal activity of phospholipase A(2) isoenzymes in postinfarct congestive heart failure.
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DOI：
10.1152/ajpcell.2001.280.3.c573
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发表时间：
2001-03
期刊：
影响因子：
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通讯作者：
J. McHowat;P. Tappia;S. Liu;R. McCrory;V. Panagia
中科院分区：
文献类型：
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作者：
J. McHowat;P. Tappia;S. Liu;R. McCrory;V. Panagia
心脏肌膜 (SL) 顺式不饱和脂肪酸敏感磷脂酶 D (cis-UFA PLD) 通过膜内释放 cis-UFA 受到 SL Ca(2+) 独立的磷脂酶 A(2) (iPLA(2)) 活性的调节。由于 PLD 衍生的磷脂酸影响细胞内 Ca(2+) 浓度和心肌细胞的收缩性能，因此 iPLA(2) 活性的变化可能会导致衰竭心脏的功能异常。我们检测了充血性心力衰竭 (CHF) 明显阶段大鼠非梗死左心室 (LV) 组织中 SL 和胞浆中 PLA(2) 免疫蛋白的表达和活性。对 CHF 动物的血流动力学评估显示左心室舒张末压升高且收缩功能丧失。在正常心脏中，免疫印迹分析显示细胞质中存在细胞质 PLA(2) (cPLA(2)) 和分泌性 PLA(2) (sPLA(2))，SL 中存在 cPLA(2) 和 iPLA(2)。细胞内PLA(2) 活性主要与Ca(2+) 无关，sPLA(2) 活性极小。 CHF增加胞质中的cPLA(2)免疫蛋白和PLA(2)活性，并降低SL iPLA(2)和cPLA(2)免疫蛋白和SL PLA(2)活性。 CHF 中 sPLA(2) 活性和丰度在细胞质中降低，在 SL 中升高。结果表明，心肌梗死后 CHF 的病理生理学本质是 SL PLA(2) 同工酶的异常，这表明 PLA(2) 介导的生物过程在 CHF 中发生了改变。
Cardiac sarcolemmal (SL) cis-unsaturated fatty acid sensitive phospholipase D (cis-UFA PLD) is modulated by SL Ca(2+)-independent phospholipase A(2) (iPLA(2)) activity via intramembrane release of cis-UFA. As PLD-derived phosphatidic acid influences intracellular Ca(2+) concentration and contractile performance of the cardiomyocyte, changes in iPLA(2) activity may contribute to abnormal function of the failing heart. We examined PLA(2) immunoprotein expression and activity in the SL and cytosol from noninfarcted left ventricular (LV) tissue of rats in an overt stage of congestive heart failure (CHF). Hemodynamic assessment of CHF animals showed an increase of the LV end-diastolic pressure with loss of contractile function. In normal hearts, immunoblot analysis revealed the presence of cytosolic PLA(2) (cPLA(2)) and secretory PLA(2) (sPLA(2)) in the cytosol, with cPLA(2) and iPLA(2) in the SL. Intracellular PLA(2) activity was predominantly Ca(2+) independent, with minimal sPLA(2) activity. CHF increased cPLA(2) immunoprotein and PLA(2) activity in the cytosol and decreased SL iPLA(2) and cPLA(2) immunoprotein and SL PLA(2) activity. sPLA(2) activity and abundance decreased in the cytosol and increased in SL in CHF. The results show that intrinsic to the pathophysiology of post-myocardial infarction CHF are abnormalities of SL PLA(2) isoenzymes, suggesting that PLA(2)-mediated bioprocesses are altered in CHF.