Computational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis.

TitleComputational Approaches to Understanding the Role of Fibroblast-Myocyte Interactions in Cardiac Arrhythmogenesis.
Publication TypeJournal Article
Year of Publication2015
AuthorsBrown, TR, Krogh-Madsen, T, Christini, DJ
JournalBiomed Res Int
Volume2015
Pagination465714
Date Published2015
ISSN2314-6141
KeywordsAction Potentials, Animals, Cell Communication, Computer Simulation, Fibroblasts, Heart Diseases, Humans, Models, Cardiovascular, Myocytes, Cardiac
Abstract

The adult heart is composed of a dense network of cardiomyocytes surrounded by nonmyocytes, the most abundant of which are cardiac fibroblasts. Several cardiac diseases, such as myocardial infarction or dilated cardiomyopathy, are associated with an increased density of fibroblasts, that is, fibrosis. Fibroblasts play a significant role in the development of electrical and mechanical dysfunction of the heart; however the underlying mechanisms are only partially understood. One widely studied mechanism suggests that fibroblasts produce excess extracellular matrix, resulting in collagenous septa. These collagenous septa slow propagation, cause zig-zag conduction paths, and decouple cardiomyocytes resulting in a substrate for arrhythmia. Another emerging mechanism suggests that fibroblasts promote arrhythmogenesis through direct electrical interactions with cardiomyocytes via gap junctions. Due to the challenges of investigating fibroblast-myocyte coupling in native cardiac tissue, computational modeling and in vitro experiments have facilitated the investigation into the mechanisms underlying fibroblast-mediated changes in cardiomyocyte action potential morphology, conduction velocity, spontaneous excitability, and vulnerability to reentry. In this paper, we summarize the major findings of the existing computational studies investigating the implications of fibroblast-myocyte interactions in the normal and diseased heart. We then present investigations from our group into the potential role of voltage-dependent gap junctions in fibroblast-myocyte interactions.

DOI10.1155/2015/465714
Alternate JournalBiomed Res Int
PubMed ID26601107
PubMed Central IDPMC4637154
Grant ListR01 EB016407 / EB / NIBIB NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
R01EB016407 / EB / NIBIB NIH HHS / United States
T32GM07739 / GM / NIGMS NIH HHS / United States