Regional imbalanced activation of the calcineurin/BAD apoptotic pathway and the PI3K/Akt survival pathway after myocardial infarction.
Regional imbalanced activation of the calcineurin/BAD apoptotic pathway and the PI3K/Akt survival pathway after myocardial infarction.
复制标题
心肌梗死后钙调神经磷酸酶/BAD 凋亡途径和 PI3K/Akt 存活途径的区域激活不平衡。
DOI：
10.1016/j.ijcard.2011.10.107
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发表时间：
2013-06-05
影响因子：
3.5
通讯作者：
Griffith, Bartley P.
中科院分区：
文献类型：
--
作者：
Li, Tieluo;Kilic, Ahmet;Wei, Xufeng;Wu, Changfu;Schwartzbauer, Gary;Yankey, G. Kwame;DeFilippi, Christopher;Bond, Meredith;Wu, Zhongjun J.;Griffith, Bartley P.
心肌梗死后心肌重构的分子机制尚不清楚。本研究的目的是在大型动物模型中研究存活途径（PI 3 K/Akt）和凋亡途径（钙调神经磷酸酶/BAD）在MI后重构中的作用。10只多赛特杂种羊左心室（LV，n=10）发生25% MI。5只绵羊用作假手术对照。区域应变由声显微测量法计算。通过免疫印迹、免疫沉淀和免疫荧光染色，在非缺血邻近区和相对于梗死的远端区评估细胞凋亡和PI 3 K/Akt和钙调神经磷酸酶/BAD通路的活化。MI后12周左室扩张、功能障碍。12周时邻近区的局部应变显著高于远区（36.6 ± 4.0%vs9.5 ± 3.6%，p < 0.05）。邻近区细胞凋亡较远区严重。PI 3 K/Akt和calcineurin/BAD通路在邻近区被激活。在邻近区域，BAD的去磷酸化和易位是明显的。菌株与Calcineurin/BAD表达之间的区域相关性表明激活是菌株相关的（Calcineurin、BAD、线粒体BAD的R2分别为0.46、0.48、0.39，p < 0.05）。MI后非缺血区PI 3 K/Akt存活和钙调神经磷酸酶/BAD凋亡通路同时激活。钙调神经磷酸酶/BAD信号通路与心肌细胞的应变有关，其不平衡激活可能是心肌梗死后进行性重构的原因之一。
The underlying molecular mechanisms of the remodeling after myocardial infarction (MI) remain unclear. The purpose of this study was to investigate the role of a survival pathway (PI3K/Akt) and an apoptosis pathway (calcineurin/BAD) in the remodeling after MI in a large animal model. Ten Dorset hybrid sheep underwent 25% MI in the left ventricle (LV, n=10). Five sheep were used as sham control. The regional strain was calculated from sonomicrometry. Apoptosis and the activation of the PI3K/Akt and calcineurin/BAD pathways were evaluated in the non-ischemic adjacent zone and the remote zone relative to infarct by immunoblotting, immunoprecipitation, and immunofluorescence staining. Dilation and dysfunction of LV were present at 12 weeks after MI. The regional strain in the adjacent zone was significantly higher than in the remote zone at 12 weeks (36.6 ± 4.0% vs 9.5 ± 3.6%, p < 0.05). Apoptosis was more severe in the adjacent zone than in the remote zone. The PI3K/Akt and calcineurin/BAD pathways were activated in the adjacent zone. Dephosphorylation and translocation of BAD were evident in the adjacent zone. Regional correlation between the strain and the expression of calcineurin/BAD indicated that the activation was strain-related (R2 = 0.46, 0.48, 0.39 for calcineurin, BAD, mitochondrial BAD, respectively, p < 0.05). The PI3K/Akt survival and calcineurin/BAD apoptotic pathways were concomitantly activated in the non-ischemic adjacent zone after MI. The calcineurin/BAD pathway is strain related and its imbalanced activation may be one of the causes of progressive remodeling after MI.
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影响因子：
37.8
作者：
GAUDRON, P;EILLES, C;ERTL, G
通讯作者：
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影响因子：
37.8
作者：
PFEFFER, MA;BRAUNWALD, E
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BRAUNWALD, E