首页> 外文期刊>American Journal of Physiology >Haptoglobin expression and activity during coronary collateralization.
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Haptoglobin expression and activity during coronary collateralization.

机译:冠状动脉抵押期间的肝珠蛋白表达和活性。

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Coronary collateral development relies on the coordinated secretion of growth factors. However, alone they are insufficient for permanent collateral growth. We utilized proteomics to identify other important proteins in the extracellular environment that could facilitate collateralization. Chronically instrumented dogs developed coronary collaterals by the repetitive occlusion method. Subendocardial (0.19 +/- 0.04, 0.27 +/- 0.06, 0.48 +/- 0.10, and 0.81 +/- 0.11 ml x min(-1) x g(-1) on days 1, 7, 14, and 21, respectively) and subepicardial (0.14 +/- 0.01, 0.36 +/- 0.06, 0.51 +/- 0.07, and 0.71 +/- 0.08 ml x min(-1) x g(-1) on days 1, 7, 14, and 21, respectively) blood flow increased in animals subjected to repetitive occlusion. Sham animals exhibited no changes in blood flow. Myocardial interstitial fluid (MIF) from both groups was analyzed by two-dimensional electrophoresis with matrix-assisted laser desorption/ionization time-of-flight identification. The acute-phase protein haptoglobin was identified in the group subjected to repetitive occlusion. ELISA of MIF showed haptoglobin to be elevated at all time points of collateral development compared with sham, with maximal production on day 7. Purified haptoglobin dose dependently stimulated endothelial cells to form tubes and vascular smooth muscle cells to migrate. Purified haptoglobin did not stimulate proliferation of either cell type. The relative contribution of haptoglobin to the chemotactic properties of MIF was tested using a neutralizing antibody. Neutralized MIF could not stimulate smooth muscle cells to migrate at any time during collateral development. Endothelial cell tube formation was inhibited after the midpoint of collateralization. Therefore, the acute-phase protein haptoglobin plays a critical role during coronary collateralization.
机译:冠状动脉侧支发育依赖于生长因子的协同分泌。但是,仅靠它们不足以实现永久抵押品增长。我们利用蛋白质组学来鉴定细胞外环境中其他可能促进抵押的重要蛋白质。长期使用仪器的狗通过重复闭塞法形成了冠状动脉侧支。心内膜下(在第1、7、14和21天分别为0.19 +/- 0.04、0.27 +/- 0.06、0.48 +/- 0.10和0.81 +/- 0.11 ml x min(-1)xg(-1) )和心外膜下(在第1、7、14和21天时为0.14 +/- 0.01、0.36 +/- 0.06、0.51 +/- 0.07和0.71 +/- 0.08 ml x min(-1)xg(-1)分别)在重复性闭塞的动物中血流量增加。假动物没有表现出血流变化。通过二维电泳和基质辅助激光解吸/电离飞行时间识别,分析了两组的心肌间质液(MIF)。在经历反复咬合的组中鉴定出急性期蛋白触珠蛋白。与假手术相比,MIF ELISA显示在侧支发育的所有时间点触珠蛋白都升高,在第7天达到最大产量。纯化的触珠蛋白剂量依赖性地刺激内皮细胞形成管,并使血管平滑肌细胞迁移。纯化的触珠蛋白不刺激任何一种细胞的增殖。使用中和抗体测试触珠蛋白对MIF趋化特性的相对贡献。中和的MIF不能在侧支发育过程中的任何时间刺激平滑肌细胞迁移。抵押的中点后,内皮细胞管的形成受到抑制。因此,急性期蛋白触珠蛋白在冠状动脉抵押术中起关键作用。

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