Role of endothelin in the induction of cardiac hypertrophy in vitro.
Role of endothelin in the induction of cardiac hypertrophy in vitro.
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DOI：
10.1371/journal.pone.0043179
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Janssen PM
中科院分区：
文献类型：
--
作者：
Bupha-Intr T;Haizlip KM;Janssen PM
内皮素（ET-1）是一种肽类激素，参与多种生物学过程，与心功能不全的发生、发展密切相关。通常，ET-1被认为是仅与观察到的肥大反应相关或与其他肥大应激结合释放的分子标记物。虽然ET-1的心肌肥厚作用已被证实，但在慢性ET-1诱导的心肌肥厚过程中，心肌的变力性仍不清楚。通过使用一种新的体外多细胞培养系统，可以观察到兔心脏小梁对1 nM ET-1反应24小时的收缩力和动力学变化。与t = 0小时时的初始力相比，ET-1处理的肌肉在24小时后显示出发展的力增加了2.5倍，而对达到峰值收缩的时间或达到90%松弛的时间没有任何影响。 由于与非ET-1处理的肌肉相比细胞宽度增加，ET-1使肌肉直径从初始大小增加12.5±3.2%。使用特异性信号传导拮抗剂，抑制NCX、CaMKII、MAPKK和IP 3可以减弱ET-1对增加的发育力的作用。然而，在这些抑制中，只有IP 3受体阻断剂不能阻止ET-1的肌肉尺寸增加。有趣的是，虽然钙调神经磷酸酶-NFAT抑制不能抑制ET-1对力量发展的影响，但它确实防止了肌肉肥大。这些结果表明，ET-1引起心肌的变力性和肥大性激活，其中这两种激活共享相同的信号通路，通过MAPK和CaMKII与NCX活性相关。
Endothelin (ET-1) is a peptide hormone mediating a wide variety of biological processes and is associated with development of cardiac dysfunction. Generally, ET-1 is regarded as a molecular marker released only in correlation with the observation of a hypertrophic response or in conjunction with other hypertrophic stress. Although the cardiac hypertrophic effect of ET-1 is demonstrated, inotropic properties of cardiac muscle during chronic ET-1-induced hypertrophy remain largely unclear. Through the use of a novel in vitro multicellular culture system, changes in contractile force and kinetics of rabbit cardiac trabeculae in response to 1 nM ET-1 for 24 hours can be observed. Compared to the initial force at t = 0 hours, ET-1 treated muscles showed a ∼2.5 fold increase in developed force after 24 hours without any effect on time to peak contraction or time to 90% relaxation. ET-1 increased muscle diameter by 12.5±3.2% from the initial size, due to increased cell width compared to non-ET-1 treated muscles. Using specific signaling antagonists, inhibition of NCX, CaMKII, MAPKK, and IP3 could attenuate the effect of ET-1 on increased developed force. However, among these inhibitions only IP3 receptor blocker could not prevent the increase muscle size by ET-1. Interestingly, though calcineurin-NFAT inhibition could not suppress the effect of ET-1 on force development, it did prevent muscle hypertrophy. These findings suggest that ET-1 provokes both inotropic and hypertrophic activations on myocardium in which both activations share the same signaling pathway through MAPK and CaMKII in associated with NCX activity.
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影响因子：
20.1
作者：
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