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Open AccessJournal ArticleDOI

Differential Behaviors of Atrial Versus Ventricular Fibroblasts A Potential Role for Platelet-Derived Growth Factor in Atrial-Ventricular Remodeling Differences

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TLDR
Atrial fibroblasts behave differently than ventricular fibro Blasts over a range of in vitro and in vivo paradigms, with atrial Fibroblast showing enhanced reactivity that may explain greater atrial fibrotic responses.
Abstract
Background— In various heart disease paradigms, atria show stronger fibrotic responses than ventricles. The possibility that atrial and ventricular fibroblasts respond differentially to pathological stimuli has not been examined. Methods and Results— We compared various morphological, secretory, and proliferative response indexes of canine atrial versus ventricular fibroblasts. Cultured atrial fibroblasts showed faster cell surface area increases, distinct morphology at confluence, and greater α-smooth muscle actin expression than ventricular fibroblasts. Atrial fibroblast proliferation ([3H]thymidine incorporation) responses were consistently greater for a range of growth factors, including fetal bovine serum, platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth factor-β1. Normal atrial tissue showed larger myofibroblast density compared with ventricular tissue, and the difference was exaggerated by congestive heart failure. Congesti...

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OtherDOI

Cardiac Fibrosis and Arrhythmogenesis.

TL;DR: Recognizing the pivotal role of fibrosis in the arrhythmogenesis has promoted clinical research on characterizing fibrosis by means of cardiac imaging or fibrosis biomarkers for clinical stratification of patients at higher risk of lethal arrhythmia, as well as preclinical research on the development of antifibrotic therapies.
Book ChapterDOI

Pathophysiology of atrial fibrillation

TL;DR: This chapter reviews the current understanding of pathophysiology of AF and identifies Pulmonary veins as the prime source for AF trigger(s) and may also be the source forAF drivers.
Journal ArticleDOI

Alcohol Consumption, Left Atrial Diameter, and Atrial Fibrillation.

TL;DR: Left atrial enlargement may be an intermediate phenotype along the causal pathway linking long‐term alcohol consumption to AF, as identified in a large, community‐based sample of participants.
Journal ArticleDOI

A distinct de novo expression of Nav1.5 sodium channels in human atrial fibroblasts differentiated into myofibroblasts

TL;DR: It is shown that human atrial fibroblast differentiation in myofibroblasts is associated with de novo expression of voltage gated sodium current and that Nav1.5 α‐subunit expression is not restricted to cardiac myocytes within the atrium.
Journal ArticleDOI

Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-β1.

TL;DR: TGF-β1 mediates selective atrial fibrosis in AF that occurs via T GF-β Receptor 1/2 and the classical Smad pathway and the differential atrial vs. ventricular fibrotic response occurs at the level of TGF- β1 receptor binding or phosphorylation.
References
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Journal ArticleDOI

Endothelial-to-mesenchymal transition contributes to cardiac fibrosis

TL;DR: It is shown that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart.
Journal ArticleDOI

Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.

TL;DR: Experimental CHF strongly promotes the induction of sustained AF by causing interstitial fibrosis that interferes with local conduction, with important potential implications for understanding, treating, and preventing AF related to CHF.
Journal ArticleDOI

Diversity, topographic differentiation, and positional memory in human fibroblasts

TL;DR: Cultured fetal and adult human fibroblasts maintained key features of HOX gene expression patterns established during embryogenesis, suggesting that HOX genes may direct topographic differentiation and underlie the detailed positional memory in fibro Blasts.
Journal ArticleDOI

PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis

TL;DR: The two PDGF null phenotypes reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis, and show that PDGF-B is required in the ontogeny of kidney mesangial cells.
Journal ArticleDOI

TGF-β induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop

TL;DR: TGF-beta induces proliferation of connective tissue cells at low concentrations by stimulating autocrine PDGF-AA secretion, which at higher concentrations of TGF- beta, is decreased by down-regulation of PDGF receptor alpha subunits and perhaps by direct growth inhibition.
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