Haptoglobin expression and activity during coronary collateralization.
Haptoglobin expression and activity during coronary collateralization.
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冠状动脉侧支期间触珠蛋白的表达和活性。
DOI：
10.1152/ajpheart.00938.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Weihrauch,Dorothee
中科院分区：
文献类型：
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作者：
Lohr,NicoleL;Warltier,DavidC;Chilian,WilliamM;Weihrauch,Dorothee
冠状动脉侧枝发育依赖于生长因子的协调分泌。然而，仅靠它们不足以实现永久的附带增长。我们利用蛋白质组学来识别细胞外环境中可以促进抵押的其他重要蛋白质。长期接受仪器治疗的狗通过重复闭塞方法形成冠状动脉。心内膜下（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·min−1·g−1）和心外膜下（0.14 ± 0.01、0.36 ± 0.06、0.51 ±在第1、7、14和21天，分别为0.07和0.71±0.08ml·min−1·g−1)，经受重复闭塞的动物的血流量增加。假手术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两组的心肌间质液（MIF）。在重复闭塞组中鉴定出急性时相蛋白触珠蛋白。 MIF 的 ELISA 显示，与假手术相比，触珠蛋白在侧枝发育的所有时间点均升高，并在第 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和血管平滑肌细胞迁移。纯化的触珠蛋白不刺激任一细胞类型的增殖。使用中和抗体测试了触珠蛋白对 MIF 趋化特性的相对贡献。中和的 MIF 不能刺激平滑肌细胞在侧枝发育过程中的任何时间迁移。侧枝化中点后内皮细胞管形成受到抑制。因此，急性时相蛋白触珠蛋白在冠状动脉侧支形成过程中起着至关重要的作用。
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·min−1·g−1ondays 1, 7, 14, and21, respectively) and subepicardial (0.14 ± 0.01, 0.36 ± 0.06, 0.51 ± 0.07, and 0.71 ± 0.08 ml·min−1·g−1ondays 1, 7, 14, and21, 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 onday 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.