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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

Cardiac Fibroblast to Myofibroblast Phenotype Conversion-An Unexploited Therapeutic Target.

TL;DR: This review will explore fibroblast to myofibroblast transition mechanisms and will consider the therapeutic potential of targeting this process as a means to arrest or even reverse cardiac fibrosis.
Journal ArticleDOI

Atrial remodeling: New pathophysiological mechanism of atrial fibrillation

TL;DR: Role of atrial remodeling has emerged as the new pathophysiological mechanism of atrian fibrillation, which will increase the probability of generating multiple atrial wavelets by enabling rapid atrial activation and dispersion of refractoriness.
Journal ArticleDOI

New Pharmacological Strategies for the Treatment of Atrial Fibrillation

TL;DR: New pharmacological approaches under investigation for the treatment of AF include agents that produce atrial‐specific or predominant inhibition of IKur, IK‐ACh, or INa, and “Upstream therapies” that effect nonion channel targets that reduce atrial structural remodeling, hypertrophy, dilatation, inflammation, oxidative injury, etc.
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Mechanisms of atrial fibrillation in athletes: what we know and what we do not know

TL;DR: This review will critically address current knowledge on the mechanisms of exercise-induced atrial fibrillation and suggest how age, sex, the presence of comorbidities and cardiovascular risk factors, and genetic individual variability might serve to flag those athletes who are at the higher risk of Exercise-induced AF.
Journal ArticleDOI

Focal adhesion kinase mediates atrial fibrosis via the AKT/S6K signaling pathway in chronic atrial fibrillation patients with rheumatic mitral valve disease.

TL;DR: It is revealed that FAK can regulate its downstream signaling to cause fibrosis in atrial tissue and activate isolated fibroblasts and this finding may contribute to the prevention of atrial fibrosis associated with chronic AF in patients with underlying cardiac disease.
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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