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ангиотензин转化酶2抑制病理性缩,心肌纤维化和心脏功能障碍

JiuChang Zhong¹, Ratnadeep Basu, Danny Guo

¹Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, T6G 2S2, Canada.

|August 4, 2010

概括

ангиотензин转化酶2 (ACE2) 通过负调节 ангиотензин II (Ang II) 来保护心脏. 重组人类ACE2 (rhACE2) 治疗减弱了Ang II诱导的心脏病和不良心脏重塑.

科学领域:

心血管科学心血管科学
酶学是一种酶学.
分子生物学分子生物学

背景情况:

ангиотензин转化酶2 (ACE2) 是一种代谢基质的酶.
假设ACE2可以负面调节血管激素II (Ang II) 介导的信号传递及其心血管效应.

研究的目的:

研究ACE2作为Ang II诱导心血管损伤的负调节者的作用.
评估复合人类ACE2 (rhACE2) 在缓解Ang II介导的心脏病方面的治疗潜力.

主要方法:

使用了ACE2淘汰赛 (Ace2(-/y)) 和野生型 (WT) 小鼠接受Ang II输液.
给格II注入的WT小鼠施用rhACE2,并评估心脏结构,功能和分子标志物.
研究了rhACE2对孤立心肌细胞和心肌纤维细胞的影响.

主要成果:

ACE2 缺乏症加剧了 Ang II 诱导的心脏纤维化和缩.
rhACE2 治疗减轻了 Ang II 诱导的心脏缩,纤维化和扩张功能障碍.
rhACE2抑制了Ang II介导的超氧化物产生和关键信号通路 (PKC,ERK,JAK2,STAT3).
在压力过重的小鼠中,rhACE2部分预防了扩张性心肌病.

结论:

ACE2作为Ang II诱导心脏病的关键负调节剂.
rhACE2有效地减轻由Ang II和压力过载引起的不良心肌重塑.
缺乏ACE2会恶化Ang II诱导的心血管病理,突出其保护作用.

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