Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Taube, David, Xu, Jiang, Yang, Xiao-Ping, Undrovinas, Albertas, Peterson, Edward, Harding, Pamela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
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
_version_ 1782278842602225664
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
work_keys_str_mv AT taubedavid fractalkinedepressescardiomyocytecontractility
AT xujiang fractalkinedepressescardiomyocytecontractility
AT yangxiaoping fractalkinedepressescardiomyocytecontractility
AT undrovinasalbertas fractalkinedepressescardiomyocytecontractility
AT petersonedward fractalkinedepressescardiomyocytecontractility
AT hardingpamela fractalkinedepressescardiomyocytecontractility