Fibroblast–myocyte coupling in the heart: Potential relevance for therapeutic interventions

Abstract

Cardiac myocyte-fibroblast electrotonic coupling is a well-established fact in vitro. Indirect evidence of its presence in vivo exists, but few functional studies have been published. This review describes the current knowledge of fibroblast-myocyte electrical signalling in the heart. Further research is needed to understand the frequency and extent of heterocellular interactions in vivo in order to gain a better understanding of their relevance in healthy and diseased myocardium. It is hoped that associated insight into myocyte-fibroblast coupling in the heart may lead to the discovery of novel therapeutic targets and the development of agents for improving outcomes of myocardial scarring and fibrosis. This article is part of a special issue entitled “Exploring Fibrosis as the Next Target for Myocardial Remodeling.”

Macrophages Facilitate Electrical Conduction in the Heart

“…Cx43-containing gap junctions electrically couple cardiomyocytes, enable electrical impulse propagation and consequently coordinate synchronous heart muscle contractions (Shibata and Yamamoto, 1977). In addition, Cx43-containing gap junctions couple cardiomyocytes with non-cardiomyocytes, which can then alter the electrophysiological properties of cardiomyocytes (Ongstad and Kohl, 2016). …”

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

“…104 Key foci of current translational research in this context are on regenerating heart muscle lost to disease by reprogramming fibroblasts to trans-differentiate into cardiomyocytes, and on reducing fibrosis or the extent of pathologic scarring that occurs in response to injury and/or disease (Box 1)…”

Striated muscle function, regeneration, and repair

“…Recent studies, however, identified endothelial cells as the predominant cell type in both mouse and human adult ventricles, representing 45–55% of the total cell count (compared with ~30% cardiomyocytes and ~15% fibroblasts), although, similar to skeletal muscle, taking up only a small fraction of the ventricular volume [28]. While evidence for electrical coupling between fibroblasts and cardiomyocytes is present in vitro [29, 30], the ability of these cell types to form functional heterocellular gap junctions in vivo is still widely debated [31, 32]. Both in skeletal and cardiac muscles, blood is delivered to cells in a hierarchical manner with primary arteries progressively bunching into smaller vessels and capillaries [33, 34].…”