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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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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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Journal ArticleDOI

The cardiac fibroblast: Origin, identity and role in homeostasis and disease.

TL;DR: This review will focus on the cardiac fibroblast, a cell type until recently ignored, but that profoundly influences heart function in its various compartments, and current advances on definitions, molecular markers and function of cardiac Fibroblasts in heart homeostasis and disease are discussed.
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Ion-channel mRNA-expression profiling: Insights into cardiac remodeling and arrhythmic substrates.

TL;DR: With increasing availability and efficiency of high-throughput PCR methods for ion-Channel subunit mRNA-expression characterization, it is likely that the application of ion-channel expression profiling will increase and that it will provide important new insights into the determinants of cardiac electrical function in both physiological and pathological situations.
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Redox control of cardiac remodeling in atrial fibrillation

TL;DR: Improving understanding of the role that ROS and redox-related (patho)-mechanisms play in the development and progression of AF may allow the development of a targeted therapy for AF that surpasses the efficacy of previous general anti-oxidative strategies.
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c-Ski, Smurf2, and Arkadia as regulators of TGF-β signaling: new targets for managing myofibroblast function and cardiac fibrosisThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

TL;DR: The study of these TGF-beta mediators is essential for future treatment of fibrotic disease, and this review highlights recent relevant findings that may impact the understanding of cardiac fibrosis.
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.
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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.
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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.
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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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