Sensing and Responding of Cardiomyocytes to Changes of Tissue Stiffness in the Diseased Heart.

Juliane Münch,Salim Abdelilah-Seyfried

doi:10.3389/fcell.2021.642840

Abstract

Cardiomyocytes are permanently exposed to mechanical stimulation due to cardiac contractility. Passive myocardial stiffness is a crucial factor, which defines the physiological ventricular compliance and volume of diastolic filling with blood. Heart diseases often present with increased myocardial stiffness, for instance when fibrotic changes modify the composition of the cardiac extracellular matrix (ECM). Consequently, the ventricle loses its compliance, and the diastolic blood volume is reduced. Recent advances in the field of cardiac mechanobiology revealed that disease-related environmental stiffness changes cause severe alterations in cardiomyocyte cellular behavior and function. Here, we review the molecular mechanotransduction pathways that enable cardiomyocytes to sense stiffness changes and translate those into an altered gene expression. We will also summarize current knowledge about when myocardial stiffness increases in the diseased heart. Sophisticated in vitro studies revealed functional changes, when cardiomyocytes faced a stiffer matrix. Finally, we will highlight recent studies that described modulations of cardiac stiffness and thus myocardial performance in vivo. Mechanobiology research is just at the cusp of systematic investigations related to mechanical changes in the diseased heart but what is known already makes way for new therapeutic approaches in regenerative biology.

Highlights

The heart is both an electrical and mechanical organ
Cardiac diseases often result in fibrotic tissue deposition or cardiomyocyte hypertrophy, two irreversible physiological changes that have a major impact on cardiac function
We focused on changes of cardiac stiffness that occur in diseased hearts

Summary

Introduction

The heart is both an electrical and mechanical organ. A heartbeat is initiated when pacemaker cells at the sinus venosus produce action potentials. Myocardial infarction and cardiomyopathies are characterized by Tissue Stiffness in Cardiac Disease cardiac remodeling, a process that includes increases of cardiomyocyte cell size (hypertrophy), fibroblast proliferation, and the deposition of ECM proteins. These changes alter tissue stiffness and extracellular mechanical stimulation of cardiomyocytes, which affects their biomechanical signaling and heart function.

Results

Conclusion