title: Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs).
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.
authors.affiliation: Division of Cardiovascular & Diabetes Research, and Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK. Electronic address: n.a.turner@leeds.ac.uk.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Turner
mesh_terms: D000067531:Alarmins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D000067531:Alarmins; D015415:Biomarkers; D058847:Inflammasomes; D051192:Receptors, Pattern Recognition
keywords: Cardiac fibroblasts; Damage-associated molecular patterns; Fibrosis; Inflammation; Innate immune system