首页> 外文期刊>American Journal of Physiology >Cigarette smoke extract inhibits angiogenesis of pulmonary artery endothelial cells: the role of calpain.
【24h】

Cigarette smoke extract inhibits angiogenesis of pulmonary artery endothelial cells: the role of calpain.

机译:香烟烟雾提取物抑制肺动脉内皮细胞的血管生成:钙蛋白酶的作用。

获取原文
获取原文并翻译 | 示例
           

摘要

Angiogenesis is an integral part of both the pulmonary inflammatory response to chronic exposure to cigarette smoke and the lung tissue remodeling associated with cigarette smoke-induced chronic obstructive pulmonary disease (COPD). To investigate the role of angiogenesis in the pathogenesis of COPD, we evaluated the effect of cigarette smoke extract (CSE) on angiogenesis of pulmonary artery endothelial cells (PAEC). Incubation of PAEC with 2.5-10% CSE resulted in a dose-dependent inhibition of endothelial monolayer wound repair. CSE also caused inhibition of tube formation on Matrigel, migration in a Boyden chamber, and proliferation of PAEC. Because calpain, a family of calcium-dependent intracellular proteases, mediates cytoskeletal signaling in endothelial motility, we explored the role of calpain in the CSE-induced inhibition of endothelial angiogenesis. Incubation of CSE resulted in a dose-dependent decrease in calpain activity. Calpain inhibitor-1, a specific inhibitor of calpain, potentiates inhibitory effect of CSE on the endothelial monolayer wound repair, tube formation, cell migration, and cell proliferation. Transfection of PAEC with antisense oligodeoxyribonucleotides of calpastatin, the major endogenous calpain inhibitor, prevented CSE-induced increase in calpastatin protein content and CSE-induced decreases in calpain activity. It also prevented CSE-induced decreases in monolayer wound repair, tube formation, and migration. These results suggest that CSE attenuates angiogenesis of PAEC and the mechanism involves inhibition of calpain. Impaired angiogenesis may impede the repair process in the lungs of cigarette smokers and contribute to the altered structural remodeling observed in the lungs of patients with cigarette smoke-related COPD.
机译:血管生成是慢性暴露于香烟烟雾的肺部炎症反应和与香烟烟雾引起的慢性阻塞性肺疾病(COPD)相关的肺组织重塑的不可或缺的部分。为了研究血管生成在COPD发病机理中的作用,我们评估了香烟烟雾提取物(CSE)对肺动脉内皮细胞(PAEC)血管生成的影响。 PAEC与2.5-10%CSE的孵育导致内皮单层伤口修复的剂量依赖性抑制。 CSE还导致抑制了基质胶上的管形成,在博登室中的迁移以及PAEC的增殖。因为钙蛋白酶,钙依赖性细胞内蛋白酶的一个家族,介导内皮运动中的细胞骨架信号传导,所以我们探讨了钙蛋白酶在CSE诱导的内皮血管生成抑制中的作用。 CSE的孵育导致钙蛋白酶活性的剂量依赖性降低。钙蛋白酶抑制剂-1(钙蛋白酶的一种特异性抑制剂)增强了CSE对内皮单层伤口修复,管形成,细胞迁移和细胞增殖的抑制作用。用钙蛋白酶的反义寡脱氧核糖核苷酸(主要的内源钙蛋白酶抑制剂)转染PAEC可以防止CSE诱导的钙蛋白酶抑制蛋白含量的增加和CSE诱导的钙蛋白酶活性降低。它还可以防止CSE诱导的单层伤口修复,管形成和迁移减少。这些结果表明,CSE减弱了PAEC的血管生成,其机制涉及抑制钙蛋白酶。血管生成受损可能会阻碍吸烟者肺部的修复过程,并导致与吸烟相关的COPD患者的肺部观察到的结构重塑发生改变。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号