van Nieuwenhoven, FA and Turner, NA (2013) The role of cardiac fibroblasts in the transition from inflammation to fibrosis following myocardial infarction. Vascular Pharmacology, 58 (3). 182 - 188. ISSN 1537-1891
Abstract
Cardiac fibroblasts (CF) play a pivotal role in the repair and remodeling of the heart that occur following myocardial infarction (MI). The transition through the inflammatory, granulation and maturation phases of infarct healing is driven by cellular responses to local levels of cytokines, chemokines and growth factors that fluctuate in a temporal and spatial manner. In the acute inflammatory phase early after MI, CF contribute to the inflammatory milieu through increased secretion of proinflammatory cytokines and chemokines, and they promote extracellular matrix (ECM) degradation by increasing matrix metalloproteinase (MMP) expression and activity. In the granulation phase, CF migrate into the infarct zone, proliferate and produce MMPs and pro-angiogenic molecules to facilitate revascularization. Fibroblasts also undergo a phenotypic change to become myofibroblasts. In the maturation phase, inflammation is reduced by anti-inflammatory cytokines, and increased levels of profibrotic stimuli induce myofibroblasts to synthesize new ECM to form a scar. The scar is contracted through the mechanical force generated by myofibroblasts, preventing cardiac dilation. In this review we discuss the transition from myocardial inflammation to fibrosis with particular focus on how CF respond to alterations in proinflammatory and profibrotic signals. By furthering our understanding of these events, it is hoped that new therapeutic interventions will be developed that selectively reduce adverse myocardial remodeling post-MI, while sparing essential repair mechanisms.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013, Elsevier. This is an author produced version of a paper published in Vascular Pharmacology. Uploaded in accordance with the publisher's self-archiving policy. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Vascular Pharmacology, [Vol 58, Issue 3, (2013) DOI: 10.1016/j.vph.2012.07.003] |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Nov 2013 10:58 |
Last Modified: | 01 Apr 2014 00:38 |
Published Version: | http://dx.doi.org/10.1016/j.vph.2012.07.003 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.vph.2012.07.003 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:76768 |