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Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target
Fibrosis occurs when the synthesis of extracellular matrix outpaces its degradation, and over time can negatively impact tissue and organ function. In the case of cardiac fibrosis, contraction and relaxation of the heart can be impaired to the point of precipitating heart failure, while at the same...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787657/ https://www.ncbi.nlm.nih.gov/pubmed/31426390 http://dx.doi.org/10.3390/jcdd6030028 |
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author | Czubryt, Michael P. |
author_facet | Czubryt, Michael P. |
author_sort | Czubryt, Michael P. |
collection | PubMed |
description | Fibrosis occurs when the synthesis of extracellular matrix outpaces its degradation, and over time can negatively impact tissue and organ function. In the case of cardiac fibrosis, contraction and relaxation of the heart can be impaired to the point of precipitating heart failure, while at the same time fibrosis can result in arrhythmias due to altered electrical properties of the myocardium. The critical event in the evolution of cardiac fibrosis is the phenotype conversion of cardiac fibroblasts to their overly-active counterparts, myofibroblasts: cells demarked by their expression of novel markers such as periostin, by their gain of contractile activity, and by their pronounced and prolonged increase in the production of extracellular matrix components such as collagens. The phenotype change is dramatic, and can be triggered by many stimuli, including mechanical force, inflammatory cytokines, and growth factors. 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. |
format | Online Article Text |
id | pubmed-6787657 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67876572019-10-16 Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target Czubryt, Michael P. J Cardiovasc Dev Dis Review Fibrosis occurs when the synthesis of extracellular matrix outpaces its degradation, and over time can negatively impact tissue and organ function. In the case of cardiac fibrosis, contraction and relaxation of the heart can be impaired to the point of precipitating heart failure, while at the same time fibrosis can result in arrhythmias due to altered electrical properties of the myocardium. The critical event in the evolution of cardiac fibrosis is the phenotype conversion of cardiac fibroblasts to their overly-active counterparts, myofibroblasts: cells demarked by their expression of novel markers such as periostin, by their gain of contractile activity, and by their pronounced and prolonged increase in the production of extracellular matrix components such as collagens. The phenotype change is dramatic, and can be triggered by many stimuli, including mechanical force, inflammatory cytokines, and growth factors. 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. MDPI 2019-08-16 /pmc/articles/PMC6787657/ /pubmed/31426390 http://dx.doi.org/10.3390/jcdd6030028 Text en © 2019 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Czubryt, Michael P. Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title | Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title_full | Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title_fullStr | Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title_full_unstemmed | Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title_short | Cardiac Fibroblast to Myofibroblast Phenotype Conversion—An Unexploited Therapeutic Target |
title_sort | cardiac fibroblast to myofibroblast phenotype conversion—an unexploited therapeutic target |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787657/ https://www.ncbi.nlm.nih.gov/pubmed/31426390 http://dx.doi.org/10.3390/jcdd6030028 |
work_keys_str_mv | AT czubrytmichaelp cardiacfibroblasttomyofibroblastphenotypeconversionanunexploitedtherapeutictarget |