Real-time monitoring of hypertrophy in HL-1 cardiomyocytes by impedance measurements reveals different modes of growth
Real-time monitoring of hypertrophy in HL-1 cardiomyocytes by impedance measurements reveals different modes of growth
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DOI：
10.1007/s10616-016-0001-3
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发表时间：
2016-10-01
期刊：
影响因子：
2.2
通讯作者：
Huber, Otmar
中科院分区：
文献类型：
--
作者：
Bloch, Laura;Ndongson-Dongmo, Bernadin;Huber, Otmar
肥厚性生长是心脏对机械负荷增加或生理应激的反应。因此，心肌细胞在长度和/或宽度上增长，以维持心泵功能。近年来，参与心肌细胞生长和重构的主要信号通路已被确定，包括钙调神经磷酸酶-NFAT和PI3K-Akt信号通路。这些通路的调控对心肌肥厚的治疗具有一定的意义。然而，对不同刺激或调节剂反应的肥大进行量化和表征是困难的。这项研究旨在测试不同的读出系统，以检测和量化肥大生长对促肥大刺激的反应差异。实时阻抗测量可以检测到内皮素、去甲肾上腺素、苯肾上腺素或BIO对肥大生长的明显差异，这是其他方法(如流式细胞仪)无法观察到的。内皮素治疗导致阻抗信号出现快速而强烈的峰值，并伴随着肌动蛋白细胞骨架的大量重新定位。肥大相关基因表达的变化被检测到，β-连环蛋白的稳定被认为是对本研究中使用的所有肥大刺激的共同反应。PI3K/mTOR抑制剂PI-103可抑制细胞肥大生长。
Hypertrophic growth is a response of the heart to increased mechanical load or physiological stress. Thereby, cardiomyocytes grow in length and/or width to maintain cardiac pump function. Major signaling pathways involved in cardiomyocyte growth and remodeling have been identified during recent years including calcineurin-NFAT and PI3K-Akt signaling. Modulation of these pathways is of certain interest for therapeutic treatment of cardiac hypertrophy. However, quantification and characterization of hypertrophy in response to different stimuli or modulators is difficult. This study aims to test different read-out systems for detection and quantification of differences in hypertrophic growth in response to prohypertrophic stimuli. Real-time impedance measurements allowed the detection of distinct differences in hypertrophic growth in response to endothelin, norepinephrine, phenylephrine or BIO, which were not observable by other methods such as flow cytometry. Endothelin treatment induced a rapid and strong peak in the impedance signal concomitant with a massive reorientation of the actin cytoskeleton. Changes in expression of hypertrophy-associated genes were detected and stabilization of beta-catenin was identified as a common response to all hypertrophic stimuli used in this study. Hypertrophic growth was blocked by the PI3K/mTOR inhibitor PI-103.