Thromboxane-Induced Contractile Response of Human Coronary Arterioles Is Diminished After Cardioplegic Arrest
Thromboxane-Induced Contractile Response of Human Coronary Arterioles Is Diminished After Cardioplegic Arrest
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DOI：
10.1016/j.athoracsur.2011.04.049
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发表时间：
2011-09-01
影响因子：
4.6
通讯作者：
Sellke, Frank W.
中科院分区：
文献类型：
--
作者：
Feng, Jun;Liu, Yuhong;Sellke, Frank W.
背景资料。本文研究了人冠脉微血管对血栓素A-2(TXA-2)的收缩反应，以及阻断和不阻断血栓素A-2受体或抑制人冠脉微血管内磷脂酶C(PLC)或蛋白激酶C-α(PKC-α)后，再灌流(CP/Rep)。检测TXA-2受体、TXA-2合成酶、PLC等TXA-2相关蛋白的蛋白/基因表达和定位。取28例心脏手术患者的右房组织，分别在冷血停跳液停跳前、停跳后再灌流10分钟后取材。从采集的组织中解剖冠状动脉小动脉(直径90~170微米)。冠脉CP/Rep后对TXA-2类似物U-46619的收缩反应较CP/Rep前显著减弱(p<；0.05)。TXA-2受体拮抗剂SQ-29548(10(-6)M)可阻断U-46619的收缩反应。预先给予PLC抑制剂U73122(10(-6)M)可显著抑制U-46619的收缩反应(p<；0.05)。给予PKC-α抑制剂萨芬戈不能影响U-46619引起的收缩。CP/REP后微循环中TXA-2受体、TXA-2合成酶、PLC-β3、磷酸化PLC-β3、PLC-γ1和PLC-Gamma 1的总蛋白水平和基因表达无明显变化，共聚焦显微镜显示微循环中TXA-2受体和PLC-β3的表达无显著差异。TXA-2受体和PLC-β3均存在于血管内皮细胞和血管内皮细胞。心脏停搏液/Rep可降低心脏手术后不久人冠状动脉对TXA-2的收缩反应。对TXA-2类似物U-46619的收缩反应是通过激活TXA-2受体和PLC实现的。(Ann Thorac Surg 2011；92：829-36)(C)2011年，胸外科学会
Background. We investigated the contractile response of human coronary microvasculature to thromboxane A-2 (TXA-2), with and without the blockade of TXA-2 receptors or the inhibition of phospholipase-C (PLC) or of protein kinase C-alpha (PKC-alpha) in the human coronary microvasculature before and after cardioplegia, followed by reperfusion (CP/Rep). Protein/gene expression and localization of TXA-2 receptors, TXA-2 synthase, PLC, and other TXA-2-related proteins was also examined.Methods. Right atrial tissue was harvested before and after cold blood cardioplegia, followed by about 10 minutes of reperfusion, from 28 patients undergoing cardiac operations. Coronary arterioles (90 to 170 mu m in diameter) were dissected from the harvested tissue.Results. The post-CP/Rep contractile response of coronary arterioles to TXA-2 analog U-46619 was significantly impaired vs pre-CP/Rep (p < 0.05). The TXA-2 receptor antagonist SQ-29548 (10(-6) M) prevented the contractile response to U-46619 (p < 0.05). Pretreatment with the PLC inhibitor U73122 (10(-6) M) significantly inhibited the U-46619-induced contractile response (p < 0.05). Administration of the PKC-alpha inhibitor safingol failed to affect U-46619-induced contraction. Total protein levels and gene expression of TXA-2 receptors, TXA-2 synthase,PLC-beta 3, phospho-PLC-beta 3, PLC-gamma 1, and phospho-PLC-gamma 1 were not altered after CP/Rep. Confocal microscopy showed no significant differences in the expression of TXA-2 receptors or PLC-beta 3 in the microcirculation. TXA-2 receptors and PLC-beta 3 were both present in smooth muscle and endothelium.Conclusions. Cardioplegia/Rep decreases the contractile response of human coronary arterioles to TXA-2 soon after cardiac operations. The contractile response to the TXA-2 analog U-46619 is through activation of TXA-2 receptors and PLC. (Ann Thorac Surg 2011;92:829-36) (C) 2011 by The Society of Thoracic Surgeons