在病理性心脏缩中,SIRT2 作为心脏保护性脱糖酶作用
Xiaoqiang Tang1, Xiao-Feng Chen1, Nan-Yu Wang1
1Department of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (X.T., X.-F.C., N.-Y.W., X.-M.W., S.-T.L., W.Z., X.Z., D.-L.H., Z.-Q.Z., H.-Z.C., D.-P.L.).
Circulation
|September 27, 2017
概括
在心力衰竭中,Sirtuin 2 (SIRT2) 蛋白被降低. 失去SIRT2会使心脏缩恶化,而过度表达则会保护心脏. 对于心力衰竭来说,SIRT2 是一个潜在的治疗点.
科学领域:
- 心血管生物学
- 疾病的分子机制
- 老龄化研究
背景情况:
- 病理性心脏缩是心力衰竭的主要危险因素.
- 驱动心脏缩的机制,特别是在衰老和压力中,尚未完全理解.
- 需要研究心脏缩中的Sirtuin 2 (SIRT2) 作用.
研究的目的:
- 研究SIRT2在与衰老相关的心脏缩中的作用.
- 检查SIRT2在血管素II (Ang II) 诱导的心脏缩中的功能.
- 阐明SIRT2影响心脏缩的分子机制.
主要方法:
- 使用野生类型,Sirt2淘汰和心脏特异性的SIRT2转基因小鼠.
- 通过衰老和Ang II输液诱导的心脏缩.
- 用于评估其与SIRT2在心脏缩中的相互作用.
- 评估心脏缩,纤维化和功能.
主要成果:
- 在高性心脏中SIRT2表达减少.
- Sirt2绝杀加剧了心脏缩和纤维化,损害了心脏功能.
- 这种SIRT2过度表达可以防止Ang II诱导的心脏缩和纤维化.
- 通过脱乙肝激酶B1 (LKB1) 来激活SIRT2的AMP激活蛋白激酶 (AMPK).
- 丧失SIRT2降低了甲胺的心脏保护作用.
结论:
- SIRT2通过LKB1脱乙激活AMPK,促进心脏健康.
- 降低SIRT2水平有助于衰老和Ang II诱导的心脏缩.
- SIRT2是治疗心脏缩和心力衰竭的潜在治疗点.
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