Turner, NA (2016) Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). Journal of Molecular and Cellular Cardiology, 94. pp. 189-200. ISSN 0022-2828
Abstract
Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1α), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2015, Elsevier Ltd. All rights reserved. This is an author produced version of a paper published in Journal of Molecular and Cellular Cardiology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Cardiac fibroblasts; Damage-associated molecular patterns; Inflammation; Fibrosis; Innate immune system |
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: | 07 Jun 2016 16:12 |
Last Modified: | 03 Nov 2016 09:06 |
Published Version: | http://doi.org/10.1016/j.yjmcc.2015.11.002 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.yjmcc.2015.11.002 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99183 |