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J Mol Cell Cardiol. 2014 May;70:9-18. doi: 10.1016/j.yjmcc.2013.10.019. Epub 2013 Nov 2.

Myofibroblasts: trust your heart and let fate decide.

Author information

1
Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
2
Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Howard Hughes Medical Institute, Cincinnati, OH 45229, USA. Electronic address: jeff.molkentin@cchmc.org.

Abstract

Cardiac fibrosis is a substantial problem in managing multiple forms of heart disease. Fibrosis results from an unrestrained tissue repair process orchestrated predominantly by the myofibroblast. These are highly specialized cells characterized by their ability to secrete extracellular matrix (ECM) components and remodel tissue due to their contractile properties. This contractile activity of the myofibroblast is ascribed, in part, to the expression of smooth muscle α-actin (αSMA) and other tension-associated structural genes. Myofibroblasts are a newly generated cell type derived largely from residing mesenchymal cells in response to both mechanical and neurohumoral stimuli. Several cytokines, chemokines, and growth factors are induced in the injured heart, and in conjunction with elevated wall tension, specific signaling pathways and downstream effectors are mobilized to initiate myofibroblast differentiation. Here we will review the cell fates that contribute to the myofibroblast as well as nodal molecular signaling effectors that promote their differentiation and activity. We will discuss canonical versus non-canonical transforming growth factor-β (TGFβ), angiotensin II (AngII), endothelin-1 (ET-1), serum response factor (SRF), transient receptor potential (TRP) channels, mitogen-activated protein kinases (MAPKs) and mechanical signaling pathways that are required for myofibroblast transformation and fibrotic disease. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ".

KEYWORDS:

Angiotensin II; Extracellular matrix; Fibrosis; Serum response factor; TGFβ; TRP channel

PMID:
24189039
PMCID:
PMC3995855
DOI:
10.1016/j.yjmcc.2013.10.019
[Indexed for MEDLINE]
Free PMC Article

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