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Fractalkine Depresses Cardiomyocyte Contractility
BACKGROUND: Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E(2) EP4 receptor sub-type (EP4 KO) exhibit reduced cardiac function. Gene array on left ventricles (LV) showed increased fractalkine, a chemokine implicated in heart failure. We therefore h...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728327/ https://www.ncbi.nlm.nih.gov/pubmed/23936109 http://dx.doi.org/10.1371/journal.pone.0069832 |
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author | Taube, David Xu, Jiang Yang, Xiao-Ping Undrovinas, Albertas Peterson, Edward Harding, Pamela |
author_facet | Taube, David Xu, Jiang Yang, Xiao-Ping Undrovinas, Albertas Peterson, Edward Harding, Pamela |
author_sort | Taube, David |
collection | PubMed |
description | BACKGROUND: Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E(2) EP4 receptor sub-type (EP4 KO) exhibit reduced cardiac function. Gene array on left ventricles (LV) showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE(2) and contributes to depressed contractility via alterations in intracellular calcium. METHODS: Fractalkine was measured in LV of 28–32 week old male EP4 KO and wild type controls (WT) by ELISA and the effect of PGE(2) on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM) from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso) stimulation. RESULTS: LV fractalkine was increased in EP4 KO mice but surprisingly, PGE(2) regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+) transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery. CONCLUSIONS: Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium. |
format | Online Article Text |
id | pubmed-3728327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37283272013-08-09 Fractalkine Depresses Cardiomyocyte Contractility Taube, David Xu, Jiang Yang, Xiao-Ping Undrovinas, Albertas Peterson, Edward Harding, Pamela PLoS One Research Article BACKGROUND: Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E(2) EP4 receptor sub-type (EP4 KO) exhibit reduced cardiac function. Gene array on left ventricles (LV) showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE(2) and contributes to depressed contractility via alterations in intracellular calcium. METHODS: Fractalkine was measured in LV of 28–32 week old male EP4 KO and wild type controls (WT) by ELISA and the effect of PGE(2) on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM) from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso) stimulation. RESULTS: LV fractalkine was increased in EP4 KO mice but surprisingly, PGE(2) regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+) transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery. CONCLUSIONS: Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium. Public Library of Science 2013-07-30 /pmc/articles/PMC3728327/ /pubmed/23936109 http://dx.doi.org/10.1371/journal.pone.0069832 Text en © 2013 Taube et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Taube, David Xu, Jiang Yang, Xiao-Ping Undrovinas, Albertas Peterson, Edward Harding, Pamela Fractalkine Depresses Cardiomyocyte Contractility |
title | Fractalkine Depresses Cardiomyocyte Contractility |
title_full | Fractalkine Depresses Cardiomyocyte Contractility |
title_fullStr | Fractalkine Depresses Cardiomyocyte Contractility |
title_full_unstemmed | Fractalkine Depresses Cardiomyocyte Contractility |
title_short | Fractalkine Depresses Cardiomyocyte Contractility |
title_sort | fractalkine depresses cardiomyocyte contractility |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3728327/ https://www.ncbi.nlm.nih.gov/pubmed/23936109 http://dx.doi.org/10.1371/journal.pone.0069832 |
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