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血管静止素:是内皮依赖血管扩张的负调节剂
Ryoji Koshida1, Jingsong Ou, Toshiro Matsunaga
1Department of Physiology, and Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee 53226, USA.
Circulation
|February 20, 2003
概括
ангиостатин 通过影响内皮氧化合成酶 (eNOS) 功能,损害血管扩张,导致超氧化物产生增加. 这种机制有助于血管静止素的抗血管性作用.
科学领域:
- 内皮细胞生物学 内皮细胞生物学
- 血管生理学 血管生理学
- 内皮功能的分子机制.
背景情况:
- 众所周知,安吉奥斯塔丁可以抑制血管生成.
- 内皮功能包括血管扩张,氧化 (NO) 生产和超氧化 (O2-) 生产.
- 热冲击蛋白90 (hsp90) 参与调节氧化合成酶 (NOS) 活性.
研究的目的:
- 为了研究血管静止素对血管扩张的影响.
- 检查hsp90-eNOS协会在血管静止素机制中的作用.
- 确定血管静止素对内皮氧化 (NO) 和超氧化 (O2-) 生成的影响.
主要方法:
- 视频显微镜评估血管扩张对乙胆 (ACh),血管内皮生长因子 (VEGF) 和帕帕维林的反应.
- 在老鼠大动脉和牛大动脉内皮细胞 (BAECs) 中测定hsp90-eNOS协会的西部抹杀或共同免疫沉.
- 在BAEC中测量NO和O2生成,分别使用化学发光和光谱测定.
主要成果:
- 安吉奥斯塔丁显著降低了ACH和VEGF介导的血管扩张,但没有帕帕维林诱导的血管扩张.
- 聚乙烯糖-超氧化物脱酶 (PEG-SOD) 治疗改善了血管扩张,这表明超氧化物的作用.
- 在BAEC中, ангиостатин降低了hsp90-eNOS关联,并增加了L-NAME可抑制的O2生成.
结论:
- ангиостатин 改变内皮氧化合成酶 (eNOS) 功能,在激活时促进 O2 生成.
- 这种eNOS活动的转变有助于受损的内皮依赖血管扩张.
- 这些发现为血管静止素的抗血管性质提供了机械的洞察力.
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