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Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure
Cardiomyocyte-specific increases in phosphorylated Hsp20 (S16D-Hsp20) to levels similar to those observed in human failing hearts are associated with early fibrotic remodeling and depressed left ventricular function, symptoms which progress to heart failure and early death. The underlying mechanisms...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488766/ https://www.ncbi.nlm.nih.gov/pubmed/31061921 http://dx.doi.org/10.1016/j.jacbts.2018.11.007 |
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author | Gardner, George T. Travers, Joshua G. Qian, Jiang Liu, Guan-Sheng Haghighi, Kobra Robbins, Nathan Jiang, Min Li, Yutian Fan, Guo-Chang Rubinstein, Jack Blaxall, Burns C. Kranias, Evangelia G. |
author_facet | Gardner, George T. Travers, Joshua G. Qian, Jiang Liu, Guan-Sheng Haghighi, Kobra Robbins, Nathan Jiang, Min Li, Yutian Fan, Guo-Chang Rubinstein, Jack Blaxall, Burns C. Kranias, Evangelia G. |
author_sort | Gardner, George T. |
collection | PubMed |
description | Cardiomyocyte-specific increases in phosphorylated Hsp20 (S16D-Hsp20) to levels similar to those observed in human failing hearts are associated with early fibrotic remodeling and depressed left ventricular function, symptoms which progress to heart failure and early death. The underlying mechanisms appear to involve translocation of phosphorylated Hsp20 to the nucleus and upregulation of interleukin (IL)-6, which subsequently activates cardiac fibroblasts in a paracrine fashion through transcription factor STAT3 signaling. Accordingly, treatment of S16D-Hsp20 mice with a rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) attenuated interstitial fibrosis and preserved cardiac function. These findings suggest that phosphorylated Hsp20 may be a potential therapeutic target in heart failure. |
format | Online Article Text |
id | pubmed-6488766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-64887662019-05-06 Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure Gardner, George T. Travers, Joshua G. Qian, Jiang Liu, Guan-Sheng Haghighi, Kobra Robbins, Nathan Jiang, Min Li, Yutian Fan, Guo-Chang Rubinstein, Jack Blaxall, Burns C. Kranias, Evangelia G. JACC Basic Transl Sci PRECLINICAL RESEARCH Cardiomyocyte-specific increases in phosphorylated Hsp20 (S16D-Hsp20) to levels similar to those observed in human failing hearts are associated with early fibrotic remodeling and depressed left ventricular function, symptoms which progress to heart failure and early death. The underlying mechanisms appear to involve translocation of phosphorylated Hsp20 to the nucleus and upregulation of interleukin (IL)-6, which subsequently activates cardiac fibroblasts in a paracrine fashion through transcription factor STAT3 signaling. Accordingly, treatment of S16D-Hsp20 mice with a rat anti-mouse IL-6 receptor monoclonal antibody (MR16-1) attenuated interstitial fibrosis and preserved cardiac function. These findings suggest that phosphorylated Hsp20 may be a potential therapeutic target in heart failure. Elsevier 2019-04-29 /pmc/articles/PMC6488766/ /pubmed/31061921 http://dx.doi.org/10.1016/j.jacbts.2018.11.007 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | PRECLINICAL RESEARCH Gardner, George T. Travers, Joshua G. Qian, Jiang Liu, Guan-Sheng Haghighi, Kobra Robbins, Nathan Jiang, Min Li, Yutian Fan, Guo-Chang Rubinstein, Jack Blaxall, Burns C. Kranias, Evangelia G. Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title | Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title_full | Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title_fullStr | Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title_full_unstemmed | Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title_short | Phosphorylation of Hsp20 Promotes Fibrotic Remodeling and Heart Failure |
title_sort | phosphorylation of hsp20 promotes fibrotic remodeling and heart failure |
topic | PRECLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488766/ https://www.ncbi.nlm.nih.gov/pubmed/31061921 http://dx.doi.org/10.1016/j.jacbts.2018.11.007 |
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