In fibrotic heart disease, fibroblast proliferation
and extracellular deposition of collagen type I are increased. In
addition, fibroblasts are known to adopt a smooth muscle-like contractile
phenotype called myofibroblasts in response to altered mechanical
loading during hypertensive heart disease or after myocardial infarction.
Fibrotic regions in the diseased heart can cause changes in normal
electrical conduction including delayed activation and conduction
block, and can act as anchors for reentrant waves. Furthermore,
with aging, increased fibrosis can lead to a spatially heterogeneous
reduction in transverse cardiomyocyte coupling and directional differences
in the propensity for conduction block at high excitation rates.
Previous studies that characterized direct interactions
between cardiomyocytes and cardiac fibroblasts in vitro and in vivo
have resulted in a controversy about the ability of these two cell
types to electrically couple and the implications that this potential
coupling would have for the function of the healthy or diseased
heart.
I study the effect of fibroblast electrotonic loading
on cardiomyocyte conduction by culturing different amounts of cardiac
fibroblasts on top of uniformly aligned (anisotropic) confluent
cardiac monolayers. I use a variety of techniques including immunohistochemical
analysis, fluorescence recovery after photobleaching (FRAP), and
optical mapping of membrane potentials to assess fibroblast phenotype
and gap junctional expression, degree of functional coupling with
cardiomyocytes, and the effect of this coupling on anisotropic electrical
propagation in cardiac monolayers.
