Automated imaging reveals a concentration dependent delay in reversibility of cardiac myocyte hypertrophy.

Journal of Molecular and Cellular Cardiology
Karen A Ryall, Jeffrey J Saucerman

Abstract

Cardiac hypertrophy is controlled by a dense signaling network with many pathways associated with cardiac myocyte growth. New large scale methodology is required to quantitatively characterize the pathways that distinguish reversible forms of hypertrophy from irreversible forms that lead to heart failure. Our automated image acquisition method records 5×5 mosaic images of fluorescent protein-labeled cardiac myocytes within each well of a 96-well plate using an automated stage and focus. Post-processing algorithms automatically identify cell edges, quantify cell phenotypes, and track cells. We uniquely applied our imaging platform to study hypertrophy reversibility in a scalable cell model. Cell area changes after washout of a dose response to the α-adrenergic receptor (αAR) agonist phenylephrine (PE) showed that hypertrophy reverses at low but not high levels of α-adrenergic signaling: a reversibility delay. Perturbations with specialized αAR antagonists, a mathematical model, and live imaging of αAR localization identify the mechanism for this reversibility delay: ligand trapping with internalized PE acting on intracellular αAR's.

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Citations

Nov 15, 2013·Journal of Molecular and Cellular Cardiology·Jason H YangJeffrey J Saucerman
Jul 22, 2015·Methods : a Companion to Methods in Enzymology·Artavazd TadevosyanBruce G Allen
Apr 20, 2014·Journal of Molecular and Cellular Cardiology·John W Elrod, Jop H van Berlo
Jun 13, 2013·Journal of Molecular and Cellular Cardiology·Clémence MerlenBruce G Allen
Mar 13, 2014·Journal of Molecular and Cellular Cardiology·Karen A RyallJeffrey J Saucerman
Apr 9, 2014·Journal of Biomolecular Screening·Shantanu SinghAuguste Genovesio
Feb 7, 2015·Journal of Cardiovascular Pharmacology·Ana F Branco, Bruce G Allen
Oct 24, 2012·The Journal of Biological Chemistry·Karen A RyallJeffrey J Saucerman
Feb 7, 2017·Cellular and Molecular Bioengineering·Cassady E RupertKareen L K Coulombe
Jul 5, 2017·The Journal of Physiological Sciences : JPS·Ali KhalilimeybodiBabak Sharif-Kashani

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