Real-time monitoring of hypertrophy in HL-1 cardiomyocytes by impedance measurements reveals different modes of growth.

Abstract

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 β-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.