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

作者：Ryall Karen A; Saucerman Jeffrey J^*

来源：Journal of Molecular and Cellular Cardiology, 2012, 53(2): 282-290.

DOI：10.1016/j.yjmcc.2012.04.016

• Cardiac hypertrophy
• Automated imaging
• alpha-Adrenergic signaling
• Cardiac myocytes
• Computational model

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 x 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 alpha-adrenergic receptor (alpha AR) agonist phenylephrine (PE) showed that hypertrophy reverses at low but not high levels of alpha-adrenergic signaling: a reversibility delay. Perturbations with specialized aAR antagonists, a mathematical model, and live imaging of alpha AR localization identify the mechanism for this reversibility delay: ligand trapping with internalized PE acting on intracellular alpha AR's.

• 出版日期2012-8