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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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OtherDOI

Atrial fibrillation: mechanisms, therapeutics, and future directions.

TL;DR: Current knowledge of AF mechanisms, therapies, and new areas of investigation are reviewed to explore the hypothesis that initiation and maintenance of AF require pathophysiological remodeling of the atria.
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Calcium in the Pathophysiology of Atrial Fibrillation and Heart Failure.

TL;DR: The latest evidence is presented showing a fundamental role for calcium in both the induction and maintenance of AF, and the effects of heart failure on atrial calcium handling that promote AF will be reviewed, including effects on both atrial myocytes and the pulmonary veins.
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Atrial fibrosis and conduction slowing in the left atrial appendage of patients undergoing thoracoscopic surgical pulmonary vein isolation for atrial fibrillation.

TL;DR: In patients with AF, thick interstitial collagen strands are associated with higher CVL and increased activation time, which demonstrates that the severity and structure of local interstitial fibrosis is associated with atrial conduction abnormalities, presenting an arrhythmogenic substrate for atrial re-entry.
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Atrial fibrillation and atrial fibrosis.

TL;DR: The role that atrial Fibrosis plays in AF, the mechanisms of atrial fibrosis, and emerging therapeutic approaches to AF aimed at attenuating atrial fibrillation are reviewed.
Journal ArticleDOI

Diffuse myocardial fibrosis: mechanisms, diagnosis and therapeutic approaches.

TL;DR: Diez et al. as discussed by the authors summarized the current knowledge on the mechanisms and detrimental consequences of diffuse myocardial fibrosis in heart failure and discussed the validity and usefulness of available imaging techniques and circulating biomarkers to assess the clinicopathological variation in this lesion and to track its clinical evolution.
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.
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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