Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
Cardiac ankyrin repeat protein attenuates cardiac hypertrophy by inhibition of ERK1/2 and TGF-β signaling pathways.
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DOI：
10.1371/journal.pone.0050436
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhu D
中科院分区：
文献类型：
--
作者：
Song Y;Xu J;Li Y;Jia C;Ma X;Zhang L;Xie X;Zhang Y;Gao X;Zhang Y;Zhu D
It has been reported that cardiac ankyrin repeat protein is associated with heart development and diseases. This study is aimed to investigate the role of CARP in heart hypertrophy in vivo. We generated a cardiac-specific CARP-overexpressing transgenic mouse. Although such animals did not display any overt physiological abnormality, they developed less cardiac hypertrophy in response to pressure overload than did wildtype mice, as indicated by heart weight/body weight ratios, echocardiographic and histological analyses, and expression of hypertrophic markers. These mice also exhibited less cardiac hypertrophy after infusion of isoproterenol. To gain a molecular insight into how CARP attenuated heart hypertrophy, we examined expression of the mitogen-activated protein kinase cascade and found that the concentrations of phosphorylated ERK1/2 and MEK were markedly reduced in the hearts of transgenic mice subjected to pressure overload. In addition, the expressions of TGF-β and phosphorylated Smad3 were significantly downregulated in the hearts of CARP Tg mice in response to pressure overload. Furthermore, addition of human TGF-β1 could reverse the inhibitory effect of CARP on the hypertrophic response induced by phenylephrine in cardiomyocytes. It was also evidenced that the inhibitory effect of CARP on cardiac hypertrophy was not attributed to apoptosis. CARP attenuates cardiac hypertrophy, in which the ERK and TGF-β pathways may be involved. Our findings highlight the significance of CARP as an anti-hypertrophic factor in therapy of cardiac hypertrophy.
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影响因子：
11.4
作者：
Bueno, OF;De Windt, LJ;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.8
作者：
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Granzier, HL
DOI：
10.1152/ajpheart.00816.2006
发表时间：
2007-05-01
影响因子：
4.8
作者：
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通讯作者：
Threadgill, David W.
影响因子：
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作者：
Cinquetti, Raffaella;Badi, Ileana;Acquatil, Francesco
通讯作者：
Acquatil, Francesco