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2015 ; 2015
(ä): 465714
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Computational Approaches to Understanding the Role of Fibroblast-Myocyte
Interactions in Cardiac Arrhythmogenesis
#MMPMID26601107
Brown TR
; Krogh-Madsen T
; Christini DJ
Biomed Res Int
2015[]; 2015
(ä): 465714
PMID26601107
show ga
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.