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HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes

BACKGROUND: We previously demonstrated the small heat shock protein, HSPB1, to prevent tachycardia remodeling in in vitro and in vivo models for Atrial Fibrillation (AF). To gain insight into its mechanism of action, we examined the protective effect of all 10 members of the HSPB family on tachycard...

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Autores principales: Ke, Lei, Meijering, Roelien A. M., Hoogstra-Berends, Femke, Mackovicova, Katarina, Vos, Michel J., Van Gelder, Isabelle C., Henning, Robert H., Kampinga, Harm H., Brundel, Bianca J. J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123278/
https://www.ncbi.nlm.nih.gov/pubmed/21731611
http://dx.doi.org/10.1371/journal.pone.0020395
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author Ke, Lei
Meijering, Roelien A. M.
Hoogstra-Berends, Femke
Mackovicova, Katarina
Vos, Michel J.
Van Gelder, Isabelle C.
Henning, Robert H.
Kampinga, Harm H.
Brundel, Bianca J. J. M.
author_facet Ke, Lei
Meijering, Roelien A. M.
Hoogstra-Berends, Femke
Mackovicova, Katarina
Vos, Michel J.
Van Gelder, Isabelle C.
Henning, Robert H.
Kampinga, Harm H.
Brundel, Bianca J. J. M.
author_sort Ke, Lei
collection PubMed
description BACKGROUND: We previously demonstrated the small heat shock protein, HSPB1, to prevent tachycardia remodeling in in vitro and in vivo models for Atrial Fibrillation (AF). To gain insight into its mechanism of action, we examined the protective effect of all 10 members of the HSPB family on tachycardia remodeling. Furthermore, modulating effects of HSPB on RhoA GTPase activity and F-actin stress fiber formation were examined, as this pathway was found of prime importance in tachycardia remodeling events and the initiation of AF. METHODS AND RESULTS: Tachypacing (4 Hz) of HL-1 atrial myocytes significantly and progressively reduced the amplitude of Ca(2+) transients (CaT). In addition to HSPB1, also overexpression of HSPB6, HSPB7 and HSPB8 protected against tachypacing-induced CaT reduction. The protective effect was independent of HSPB1. Moreover, tachypacing induced RhoA GTPase activity and caused F-actin stress fiber formation. The ROCK inhibitor Y27632 significantly prevented tachypacing-induced F-actin formation and CaT reductions, showing that RhoA activation is required for remodeling. Although all protective HSPB members prevented the formation of F-actin stress fibers, their mode of action differs. Whilst HSPB1, HSPB6 and HSPB7 acted via direct prevention of F-actin formation, HSPB8-protection was mediated via inhibition of RhoA GTPase activity. CONCLUSION: Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. The cardioprotective role for multiple HSPB members indicate a possible therapeutic benefit of compounds able to boost the expression of single or multiple members of the HSPB family.
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spelling pubmed-31232782011-06-30 HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes Ke, Lei Meijering, Roelien A. M. Hoogstra-Berends, Femke Mackovicova, Katarina Vos, Michel J. Van Gelder, Isabelle C. Henning, Robert H. Kampinga, Harm H. Brundel, Bianca J. J. M. PLoS One Research Article BACKGROUND: We previously demonstrated the small heat shock protein, HSPB1, to prevent tachycardia remodeling in in vitro and in vivo models for Atrial Fibrillation (AF). To gain insight into its mechanism of action, we examined the protective effect of all 10 members of the HSPB family on tachycardia remodeling. Furthermore, modulating effects of HSPB on RhoA GTPase activity and F-actin stress fiber formation were examined, as this pathway was found of prime importance in tachycardia remodeling events and the initiation of AF. METHODS AND RESULTS: Tachypacing (4 Hz) of HL-1 atrial myocytes significantly and progressively reduced the amplitude of Ca(2+) transients (CaT). In addition to HSPB1, also overexpression of HSPB6, HSPB7 and HSPB8 protected against tachypacing-induced CaT reduction. The protective effect was independent of HSPB1. Moreover, tachypacing induced RhoA GTPase activity and caused F-actin stress fiber formation. The ROCK inhibitor Y27632 significantly prevented tachypacing-induced F-actin formation and CaT reductions, showing that RhoA activation is required for remodeling. Although all protective HSPB members prevented the formation of F-actin stress fibers, their mode of action differs. Whilst HSPB1, HSPB6 and HSPB7 acted via direct prevention of F-actin formation, HSPB8-protection was mediated via inhibition of RhoA GTPase activity. CONCLUSION: Overexpression of HSPB1, as well as HSPB6, HSPB7 and HSPB8 independently protect against tachycardia remodeling by attenuation of the RhoA GTPase pathway at different levels. The cardioprotective role for multiple HSPB members indicate a possible therapeutic benefit of compounds able to boost the expression of single or multiple members of the HSPB family. Public Library of Science 2011-06-24 /pmc/articles/PMC3123278/ /pubmed/21731611 http://dx.doi.org/10.1371/journal.pone.0020395 Text en Ke 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
Ke, Lei
Meijering, Roelien A. M.
Hoogstra-Berends, Femke
Mackovicova, Katarina
Vos, Michel J.
Van Gelder, Isabelle C.
Henning, Robert H.
Kampinga, Harm H.
Brundel, Bianca J. J. M.
HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title_full HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title_fullStr HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title_full_unstemmed HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title_short HSPB1, HSPB6, HSPB7 and HSPB8 Protect against RhoA GTPase-Induced Remodeling in Tachypaced Atrial Myocytes
title_sort hspb1, hspb6, hspb7 and hspb8 protect against rhoa gtpase-induced remodeling in tachypaced atrial myocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123278/
https://www.ncbi.nlm.nih.gov/pubmed/21731611
http://dx.doi.org/10.1371/journal.pone.0020395
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