通过一氧化碳调动依赖于氧化的骨髓原始体,增强了血管损伤后的内皮修复
Barbara Wegiel1, David J Gallo, Kathleen G Raman
1Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Circulation
|January 20, 2010
概括
一氧化碳 (CO) 加快了内皮细胞 (EC) 的增殖和损伤后的血管修复. 这个过程依赖于氧化 (NO) 的产生和EC原生细胞的招募.
科学领域:
- 血管生物学 血管生物学
- 蜂信号传输是如何进行的
- 再生医学是一种再生医学.
背景情况:
- 一氧化碳 (CO) 是一种已知的血管恒温分子.
- 氧化碳对血管光滑肌细胞表现出抗增殖作用,防止血管塑性手术后的狭窄.
- 碳化合物的对再内皮质形成的影响仍未得到研究.
研究的目的:
- 研究一氧化碳 (CO) 对血管损伤后内皮细胞 (EC) 增殖和再内皮化的影响.
- 阐明CO对EC和血管修复作用的潜在分子机制.
主要方法:
- 动物模型的动脉损伤被利用.
- CO是作为气体或CO释放分子的.
- 在体外和体内测试评估了EC增殖,运动性和再内皮质化.
- 分析了包括RhoA,Akt和氧化 (NO) 合成酶在内的分子信号通路.
- 骨髓衍生的EC原始体的动员和招募被量化.
- 在野生类型和eNOS的小鼠中进行了实验.
主要成果:
- 在试验室中,CO显著增强了EC增殖和运动率 (> 50%),并在体内加速重新内皮质化 (4日与6日对比).
- CO激活了RhoA,导致下游Akt酸化,并增加了ECs的NO生成.
- CO通过视网母细胞瘤酸化促进细胞循环的进展,部分依赖于NO.
- 碳化合物增加了骨髓衍生的EC原体的调动 (4倍),并将其沉积在受伤部位.
- CO未能在eNOS的小鼠中促进EC修复,这表明NO的关键作用.
结论:
- 一氧化碳 (CO) 加快了内皮细胞 (EC) 的增殖和损伤后的血管修复.
- 二氧化碳的再生效应取决于氧化 (NO) 的产生.
- 加强从骨髓中获得的内皮前代细胞的招募对于CO介导的血管修复至关重要.
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