Ryanodine Receptor Type 2 Is Required for the Development of Pressure Overload-Induced Cardiac Hypertrophy
Ryanodine Receptor Type 2 Is Required for the Development of Pressure Overload-Induced Cardiac Hypertrophy
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压力过载引起的心脏肥大的发生需要 2 型瑞尼定受体
DOI：
10.1161/hypertensionaha.111.173500
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发表时间：
2011-12
期刊：
影响因子：
8.3
通讯作者：
Ge, Junbo
中科院分区：
文献类型：
--
作者：
Shiojima, Ichiro;Wang, Yuqi;Komuro, Issei;Ge, Junbo
Ryanodine 受体 2 型 (RyR-2) 介导肌浆网 Ca2+ 释放，有助于心肌收缩功能。然而，RyR-2 在心脏肥大发展中的作用尚不完全清楚。在此，分析了 RyR-2 基因减少或未减少的小鼠（分别为 RyR-2 +/- 和野生型）。在基线时，RyR-2 +/- 和野生型小鼠之间的心肌细胞和心脏形态以及心肌收缩力没有差异，尽管在分离的 RyR-2 +/- 心肌细胞中肌浆网释放的 Ca2+ 受到损害。在由横主动脉收缩引起的为期 3 周的压力超负荷期间，分离的 RyR-2 +/- 心肌细胞表现出更多的 Ca2+ 瞬时振幅、收缩期细胞内 Ca2+ 浓度增加率和缩短分数百分位数的减少，并且 RyR-2 +/- 小鼠的心脏表现出较少的代偿性肥大、纤维化和收缩性；心肌细胞凋亡较多，自噬较少；与野生型相比，血管生成也有类似的减少。此外，横主动脉收缩诱导的钙调神经磷酸酶、细胞外信号调节蛋白激酶和蛋白激酶 B/Akt 的激活增加，但不是 Ca2+/钙调蛋白依赖性蛋白激酶 II 的激活增加，并且其在野生型小鼠心脏中的下游靶标在 RyR-2 +/- 1 中被消除，表明 RyR-2 是钙调神经磷酸酶、细胞外信号调节蛋白激酶和 Akt 的调节剂，但不是压力超载期间钙调蛋白依赖性蛋白激酶 II 激活。综上所述，我们的数据表明，RyR-2 通过调节肌浆网 Ca2+ 释放，有助于心脏肥大的发展和压力超负荷期间心脏功能的适应。激活钙调神经磷酸酶、细胞外信号调节蛋白激酶和 Akt；和心肌细胞的存活率。
Ryanodine receptor type 2 (RyR-2) mediates Ca2+ release from sarcoplasmic reticulum and contributes to myocardial contractile function. However, the role of RyR-2 in the development of cardiac hypertrophy is not completely understood. Here, mice with or without reduction of RyR-2 gene (RyR-2 +/− and wild-type, respectively) were analyzed. At baseline, there was no difference in morphology of cardiomyocyte and heart and cardiac contractility between RyR-2 +/− and wild-type mice, although Ca2+ release from sarcoplasmic reticulum was impaired in isolated RyR-2 +/− cardiomyocytes. During a 3-week period of pressure overload, which was induced by constriction of transverse aorta, isolated RyR-2 +/− cardiomyocytes displayed more reduction of Ca2+ transient amplitude, rate of an increase in intracellular Ca2+ concentration during systole, and percentile of fractional shortening, and hearts of RyR-2 +/− mice displayed less compensated hypertrophy, fibrosis, and contractility; more apoptosis with less autophagy of cardiomyocytes; and similar decrease of angiogenesis as compared with wild-type ones. Moreover, constriction of transverse aorta-induced increases in the activation of calcineurin, extracellular signal-regulated protein kinases, and protein kinase B/Akt but not that of Ca2+/calmodulin-dependent protein kinase II, and its downstream targets in the heart of wild-type mice were abolished in the RyR-2 +/− one, suggesting that RyR-2 is a regulator of calcineurin, extracellular signal-regulated protein kinases, and Akt but not of calmodulin-dependent protein kinase II activation during pressure overload. Taken together, our data indicate that RyR-2 contributes to the development of cardiac hypertrophy and adaptation of cardiac function during pressure overload through regulation of the sarcoplasmic reticulum Ca2+ release; activation of calcineurin, extracellular signal-regulated protein kinases, and Akt; and cardiomyocyte survival.
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影响因子：
8.3
作者：
Tsutomu Yamazaki;Issei Komuro;Yunzeng Zou;S. Kudoh;I. Shiojima;T. Mizuno;Yukio Hiroi;R. Nagai;Yoshio Yazaki
通讯作者：
Tsutomu Yamazaki;Issei Komuro;Yunzeng Zou;S. Kudoh;I. Shiojima;T. Mizuno;Yukio Hiroi;R. Nagai;Yoshio Yazaki
DOI：
10.1172/jci24569
发表时间：
2005-03
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
R. Foo;K. Mani;R. Kitsis
通讯作者：
R. Foo;K. Mani;R. Kitsis
影响因子：
64.5
作者：
Marx, SO;Reiken, S;Marks, AR
通讯作者：
Marks, AR
影响因子：
5.3
作者：
Sanna, B;Bueno, OF;Molkentin, JD
通讯作者：
Molkentin, JD
DOI：
10.1161/hc2601.090987
发表时间：
2001-07
期刊：
Circulation: Journal of the American Heart Association
影响因子：
--
作者：
Y. Zou;A. Yao;Weidong Zhu;S. Kudoh;Y. Hiroi;M. Shimoyama;Hiroki Uozumi;O. Kohmoto;Toshiyuki Takahashi
通讯作者：
Y. Zou;A. Yao;Weidong Zhu;S. Kudoh;Y. Hiroi;M. Shimoyama;Hiroki Uozumi;O. Kohmoto;Toshiyuki Takahashi