年龄降低了通过降低缺氧诱导因子1alpha稳定在缺血期间的内皮原生细胞招募
Eric I Chang1, Shang A Loh, Daniel J Ceradini
1Department of Surgery, Stanford University, Stanford, CA 94305, USA.
Circulation
|November 28, 2007
概括
衰老通过影响内皮前体细胞 (EPCs) 损害了身体形成新血管的能力. 衰老的组织无法激活低氧诱导因子1-α反应,阻碍了新血管和组织修复.
科学领域:
- 老年学和再生医学的研究.
- 血管生物学和生理学
- 衰老的细胞和分子机制.
背景情况:
- 晚年与神经血管功能受损有关,神经血管是组织修复和生存的关键过程.
- 内皮原生细胞 (EPC) 在新血管化中起着至关重要的作用,使它们成为了解与年龄相关的血管功能障碍的关键焦点.
研究的目的:
- 调查衰老对EPC招募及其融入新血管的影响.
- 阐明导致与年龄相关的新血管化缺陷的潜在分子机制.
主要方法:
- 在老年和年轻小鼠中利用缺血模型来评估新血管化和EPC动员.
- 采用性别不匹配的骨髓移植来区分骨髓衍生和组织内在的血管生成贡献.
- 分析了缺氧诱导因子1-alpha (HIF-1α) 在缺血组织中的稳定和降解途径.
主要成果:
- 与年轻小鼠相比,老年小鼠表现出明显减少的EPC动员和受损的组织存活率,与减少的组织输液和血管密度相关.
- 骨髓移植证实了老年小鼠骨髓中介血管生成的缺陷.
- 衰老导致缺血组织中HIF-1α稳定性下降,原因是prolyl氧酶活性增加和蛋白质体降解,导致缺氧反应减弱和SDF-1和VEGF等关键血管生成因子水平降低.
结论:
- 衰老会损害EPC向缺血部位的流通,这并不是由于内在的EPC缺陷,而是由于老化的组织无法正确激活缺氧诱导因子1-alpha (HIF-1α) 介导的缺氧反应.
- 铁化剂德费罗胺可以通过稳定HIF-1α来逆转与年龄相关的缺陷,从而提高组织存活率.
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