Automated Imaging Reveals a Concentration Dependent Delay in Reversibility of Cardiac Myocyte Hypertrophy

Overview

Journal J Mol Cell Cardiol

Specialty Cardiology & Vascular Diseases

Date 2012 May 12

PMID 22575844

Citations 11

Authors

Karen A Ryall

Jeffrey J Saucerman

Affiliations

Soon will be listed here.

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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