Carabin Protects Against Cardiac Hypertrophy by Blocking Calcineurin, Ras, and Ca2+/Calmodulin-Dependent Protein Kinase II Signaling
Carabin Protects Against Cardiac Hypertrophy by Blocking Calcineurin, Ras, and Ca2+/Calmodulin-Dependent Protein Kinase II Signaling
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DOI：
10.1161/circulationaha.114.010686
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发表时间：
2015-01-27
期刊：
影响因子：
37.8
通讯作者：
Lezoualc'h, Frank
中科院分区：
文献类型：
--
作者：
Bisserier, Malik;Berthouze-Duquesnes, Magali;Lezoualc'h, Frank
背景：心脏肥厚是心衰临床过程中的早期标志，受多种信号通路调节。然而，负调控这些信号转导途径的分子机制仍然知之甚少。方法和结果：在这里，我们表征了Carabin，一种在心肌细胞中表达的蛋白，在心脏肥厚和人类心力衰竭中下调。主动脉横缩后4周，Carabin缺陷（-/-）小鼠出现了严重的心脏肥厚，并表现出明显的缩短时间减少(14.6 +/- 1.6%，而野生型加主动脉横缩小鼠为27.6 +/- 1.4%
Background-Cardiac hypertrophy is an early hallmark during the clinical course of heart failure and is regulated by various signaling pathways. However, the molecular mechanisms that negatively regulate these signal transduction pathways remain poorly understood.Methods and Results-Here, we characterized Carabin, a protein expressed in cardiomyocytes that was downregulated in cardiac hypertrophy and human heart failure. Four weeks after transverse aortic constriction, Carabin-deficient (Carabin(-/-)) mice developed exaggerated cardiac hypertrophy and displayed a strong decrease in fractional shortening (14.6 +/- 1.6% versus 27.6 +/- 1.4% in wild type plus transverse aortic constriction mice; P