血管氧化应激增强实验性动脉瘤的进展和血管生成
Jaikirshan J Khatri1, Chad Johnson, Richard Magid
1Division of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Circulation
|January 28, 2004
概括
在光滑肌肉细胞中,氧化应激通过增加血管内皮生长因子 (VEGF) 来促进动脉损伤生长和血管生成. 这一途径可能会导致人类动脉瘤的进展和不稳定.
科学领域:
- 心血管生物学 心血管生物学
- 血管生物学 血管生物学
- 氧化压力研究研究 氧化压力研究
背景情况:
- 氧化应激与各种病理有关,但其在动脉损伤进展中的直接作用尚未完全理解.
- 研究氧化应激和动脉疾病之间的因果关系对于开发有效的治疗方法至关重要.
研究的目的:
- 为了确定平滑肌肉细胞 (SMC) 向氧化应激对动脉损伤进展的影响.
- 阐明将氧化应激与动脉病变中的血管生成联系起来的分子机制.
主要方法:
- 在SMC中过度表达p22phox的野生类型和转基因小鼠中比较动脉病变进展.
- 测量过氧化 (H2O2),血管内皮生长因子 (VEGF) 和缺氧诱导因子 (HIF) -1alpha水平.
- 在实验室中与SMC和内皮细胞进行共同培养实验.
- 评估抗氧化剂ebselen的作用.
主要成果:
- 与野生类型小鼠相比,具有SMC向氧化应激的转基因小鼠表现出明显更大的动脉病变.
- 在转基因小鼠的病变中观察到高水平的H2O2,VEGF和HIF-1alpha.
- 来自转基因小鼠的SMCs在体外促进了血管生成,而ebselen在体内抑制了病变进展和血管生成.
结论:
- 在SMC中的氧化应激可以启动血管性开关,驱动实验性斑块进展和血管生成.
- 这种涉及氧化应激,VEGF和血管生成的新途径可能在人类动脉瘤的进展和不稳定中发挥作用.
- 向氧化应激是一种潜在的治疗策略,用于管理动脉损伤的发展.
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