Circulation. 2008;117:1621
doi: 10.1161/CIRCULATIONAHA.107.189184
(Circulation. 2008;117:1621.)
© 2008 American Heart Association, Inc.
Clinical Summaries
An extract of the first 250 words of the full text is provided, because this article has no abstract.
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Differential Behaviors of Atrial Versus Ventricular Fibroblasts: A Potential Role for Platelet-Derived Growth Factor in Atrial-Ventricular Remodeling Differences
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Cardiac tissue fibrosis is important in the progression of heart
disease and plays an important role in cardiac arrhythmogenesis,
particularly for atrial fibrillation. In a variety of cardiac
disease models, atrial fibrosis is much more prominent than
fibrosis in the ventricles, even when the profibrotic stimulus
appears to be operating comparably at both the atrial and ventricular
levels. This study examined the hypothesis that differences
between atrial and ventricular fibroblast properties contribute
to the predominant atrial fibrotic phenotype. To assess this
possibility, we compared morphological, secretory, and proliferative
responses of canine atrial versus ventricular fibroblasts. Atrial
fibroblasts showed in vitro and in vivo behaviors indicating
a greater tendency to activated myofibroblast dedifferentiation.
Atrial fibroblast proliferation responses were consistently
greater than ventricular responses for a variety of growth factors,
including fetal bovine serum, platelet-derived growth factor,
basic fibroblast growth factor, angiotensin II, endothelin-1,
and transforming growth factor-β
1. Atrial tissue showed
larger myofibroblast density than ventricular tissue, particularly
in the presence of congestive heart failure. Congestive heart
failure atria had more active fibroblast division rates and
enhanced gene expression of fibroblast-selective markers compared
with ventricles. Gene microarrays revealed 225 differentially
expressed transcript probe sets between paired atrial and ventricular
fibroblast samples, including extracellular matrix, cell signaling,
and metabolism genes, and identified platelet-derived growth
factor as a potential contributor to atrial-ventricular fibroblast
differences. Platelet-derived growth factor inhibition eliminated
atrial-ventricular fibroblast proliferative response differences.
Our results suggest that important differences exist in properties
of atrial versus ventricular fibroblasts, that these differences
contribute to
. . . [Full Text of this Article]