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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

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

Absence of natriuretic peptide clearance receptor attenuates TGF-β1-induced selective atrial fibrosis and atrial fibrillation.

TL;DR: The differential response to TGF-β1 stimulated fibrosis between the atria and ventricle are in part mediated by the abundance of NPR-C receptors in the atrium.
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Atrial Cardiomyopathy: Pathophysiology and Clinical Consequences.

TL;DR: In this paper, the authors summarize the underlying pathophysiology and remodeling processes observed in the development of an atrial cardiomyopathy, thrombogenesis, and atrial fibrillation.
Journal ArticleDOI

Cardiac fibroblast diversity in health and disease.

TL;DR: It is proposed that at least in part, the observed heterogeneity is related to the existence of a differentiation cascade within stromal cells, and that although fibrogenic cells from different organs overlap in many properties, they still possess organ-specific transcriptional signatures and differentiation biases that make them functionally distinct.
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A New Therapeutic Framework for Atrial Fibrillation Drug Development.

TL;DR: It is argued that current drugs for AF are inadequate because of an oversimplified system for patient classification and the development of drugs that do not interdict underlying disease mechanisms, and adopted a new framework for patient subsegmentation based on pathophysiological, genetic, and molecular subsets will improve success rates of clinical trials and advance drugs that reduce the individual patient and public health burden of AF.
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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