Systems Modeling of Cardiomyocyte Mechanobiology

Kyle S Buchholz,Philip M Tan,Jeffrey H Omens,Shulin Cao,Yasser Aboelkassem,Andrew

doi:10.32604/mcb.2019.05693

Abstract

In this article, we summarize our systems model of cardiomyocyte mechano-signaling published in PLoS Computational Biology and discuss new approaches to extending these models to predict cardiac myocyte gene expression in response to stretch.

Highlights

Cardiac muscle cells can sense and respond to mechanical cues, and this ability is a fundamental feature of cardiac hypertrophy and remodeling in response to altered hemodynamic loads [Omens, McCulloch and Lorenzen-Schmidt (2007)]
A sensitivity analysis showed that calcium, actin, Ras, Raf1, 1 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. 2 Departments of Bioengineering and Medicine, University of California San Diego, La Jolla, CA, USA. * Corresponding Author: Andrew D
PI3K, and JAK were the dominant regulators in the network and the main mediators of expression stimulated by angiotensin receptors, integrins, and calcium channels

Summary

Introduction

Cardiac muscle cells can sense and respond to mechanical cues, and this ability is a fundamental feature of cardiac hypertrophy and remodeling in response to altered hemodynamic loads [Omens, McCulloch and Lorenzen-Schmidt (2007)]. Many mechano-sensitive proteins and signaling molecules have been identified in cardiac myocytes [Zou, Akazawa, Qin et al (2004)]. It remains poorly understood how the downstream signaling pathways integrated into hypertrophy and remodeling responses [Zablocki and Sadoshima (2013)]. Computational systems models can quantify cell signaling and elucidate mechanisms, but they had not previously been developed for cardiac myocyte mechanosignaling. We reconstructed and tested the first computational model of the cardiac mechanosignaling network and used it to identify regulators if the stretch-induced hypertrophic response [Tan, Buchholz, Omens et al (2017)]

Methods

Results

Discussion