Passive ventricular remodeling in cardiac disease: focus on heterogeneity.

Elise L. Kessler,Mohamed Boulaksil,Harold V. M. van Rijen,Marc A. Vos,Toon A. B. van Veen

doi:10.3389/fphys.2014.00482

Abstract

Passive ventricular remodeling is defined by the process of molecular ventricular adaptation to different forms of cardiac pathophysiology. It includes changes in tissue architecture, such as hypertrophy, fiber disarray, alterations in cell size and fibrosis. Besides that, it also includes molecular remodeling of gap junctions, especially those composed by Connexin43 proteins (Cx43) in the ventricles that affect cell-to-cell propagation of the electrical impulse, and changes in the sodium channels that modify excitability. All those alterations appear mainly in a heterogeneous manner, creating irregular and inhomogeneous electrical and mechanical coupling throughout the heart. This can predispose to reentry arrhythmias and adds to a further deterioration into heart failure. In this review, passive ventricular remodeling is described in Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM), and Arrhythmogenic Cardiomyopathy (ACM), with a main focus on the heterogeneity of those alterations mentioned above.

Highlights

The lifelong purpose of the heart is maintenance of cardiac output and supply of all organs with an appropriate amount of oxygen and nutrients
Heterogeneous alterations in three factors contribute to increase the propensity to arrhythmias and to develop heart failure: (1) tissue architecture such as hypertrophy, fibrosis, fiber disarray, and cell size, (2) electrical coupling by means of gap junctions and especially those composed of Connexin43 proteins (Cx43), and (3) electrical excitability due to changes in sodium channels that are mainly composed of Nav1.5 (Kleber and Rudy, 2004; van Rijen et al, 2006; Bowers et al, 2010)
In an UM-X7.1 cardiomyopathic hamster model of Hypertrophic Cardiomyopathy (HCM) hypertrophy, a decrease in Cx43 mRNA, increased amounts of fibrosis and arrhythmias were seen after 20 weeks (Ambra et al, 2002; Sato et al, 2008)

Summary

Introduction

The lifelong purpose of the heart is maintenance of cardiac output and supply of all organs with an appropriate amount of oxygen and nutrients. Passive remodeling is defined as the chronic molecular and structural adaptations in ventricular cardiomyocytes and alterations in gene expression as induced by different forms of heart disease.

Results

Conclusion