Calcium-independent phospholipase A2-catalyzed plasmalogen hydrolysis in hypoxic human coronary artery endothelial cells.
Calcium-independent phospholipase A2-catalyzed plasmalogen hydrolysis in hypoxic human coronary artery endothelial cells.
复制标题
缺氧人冠状动脉内皮细胞中不依赖钙的磷脂酶 A2 催化缩醛磷脂水解。
DOI：
10.1152/ajpcell.00120.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
McHowat,Jane
中科院分区：
文献类型：
--
作者：
Meyer,MaureenC;McHowat,Jane
凝血酶刺激人冠状动脉内皮细胞（HCAEC）导致膜相关、钙非依赖性磷脂酶A2（iPLA 2）活化，该酶选择性水解膜缩醛磷脂。动脉粥样硬化斑块的破裂和冠状血管系统的闭塞导致冠状动脉缺血事件，其中缺血区域中的HCAEC除了暴露于凝血酶之外还将暴露于氧张力的急剧降低。我们将HCAEC暴露于存在或不存在凝血酶刺激的缺氧环境中，并测量iPLA 2活化、膜磷脂水解和生物活性磷脂代谢产物的积累。HCAEC暴露于缺氧、凝血酶刺激或这两种条件的组合，表现出iPLA 2活性的增加和从血浆胆碱释放花生四烯酸的增加。凝血酶刺激的常氧HCAEC没有导致胆碱溶血磷脂的积累，但缺氧单独和与凝血酶刺激的组合导致了显着的积累溶血磷脂酰胆碱（LPlsCho）。我们建议，缺氧的存在下抑制LPlsCho catastrophe，至少在一定程度上，由于长链酰基肉毒碱的积累。LPlsCho的积累需要产量增加和催化剂减少的结合。用溴烯醇内酯预处理以抑制iPLA 2阻断膜磷脂水解和膜磷脂衍生代谢产物的产生。iPLA 2活性的增加和随后在暴露于缺氧或凝血酶刺激的HCAEC中膜磷脂衍生代谢物的积累，特别是在组合中，在动脉粥样硬化/血栓形成和随后的心肌缺血中的炎症和血管生成中具有重要意义。
Thrombin stimulation of human coronary artery endothelial cells (HCAEC) results in activation of a membrane-associated, calcium-independent phospholipase A2(iPLA2) that selectively hydrolyzes membrane plasmalogen phospholipids. Rupture of an atherosclerotic plaque and occlusion of the coronary vasculature results in a coronary ischemic event in which HCAEC in the ischemic area would be exposed to dramatic decreases in oxygen tension in addition to thrombin exposure. We exposed HCAEC to hypoxia in the presence or absence of thrombin stimulation and measured iPLA2activation, membrane phospholipid hydrolysis, and the accumulation of biologically active phospholipid metabolites. HCAEC exposed to hypoxia, thrombin stimulation, or a combination of the two conditions demonstrated an increase in iPLA2activity and an increase in arachidonic acid release from plasmenylcholine. Thrombin stimulation of normoxic HCAEC did not result in an accumulation of choline lysophospholipids, but hypoxia alone and in combination with thrombin stimulation led to a significant accumulation of lysoplasmenylcholine (LPlsCho). We propose that the presence of hypoxia inhibits LPlsCho catabolism, at least in part, as a result of the accumulation of long-chain acylcarnitines. The combination of increased production and decreased catabolism of LPlsCho is necessary for its accumulation. Pretreatment with bromoenol lactone to inhibit iPLA2blocked membrane phospholipid hydrolysis and production of membrane phospholipid-derived metabolites. The increase in iPLA2activity and the subsequent accumulation of membrane phospholipid-derived metabolites in HCAEC exposed to hypoxia or thrombin stimulation alone, and particularly in combination, have important implications in inflammation and arrhythmogenesis in atherosclerosis/thrombosis and subsequent myocardial ischemia.