Cargando…

Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing

AIMS: The role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2(−/−)) protected against cardiac hypertrophy and failure. However, in UCP2(−/−) mice increased proliferat...

Descripción completa

Detalles Bibliográficos
Autores principales: Esfandiary, Azadeh, Kutsche, Hanna S, Schreckenberg, Rolf, Weber, Martin, Pak, Oleg, Kojonazarov, Baktybek, Sydykov, Akylbek, Hirschhäuser, Christine, Wolf, Annemarie, Haag, Daniela, Hecker, Matthias, Fink, Ludger, Seeger, Werner, Ghofrani, Hossein A, Schermuly, Ralph T, Weißmann, Norbert, Schulz, Rainer, Rohrbach, Susanne, Li, Ling, Sommer, Natascha, Schlüter, Klaus-Dieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529920/
https://www.ncbi.nlm.nih.gov/pubmed/30850841
http://dx.doi.org/10.1093/cvr/cvz049
_version_ 1783420509112762368
author Esfandiary, Azadeh
Kutsche, Hanna S
Schreckenberg, Rolf
Weber, Martin
Pak, Oleg
Kojonazarov, Baktybek
Sydykov, Akylbek
Hirschhäuser, Christine
Wolf, Annemarie
Haag, Daniela
Hecker, Matthias
Fink, Ludger
Seeger, Werner
Ghofrani, Hossein A
Schermuly, Ralph T
Weißmann, Norbert
Schulz, Rainer
Rohrbach, Susanne
Li, Ling
Sommer, Natascha
Schlüter, Klaus-Dieter
author_facet Esfandiary, Azadeh
Kutsche, Hanna S
Schreckenberg, Rolf
Weber, Martin
Pak, Oleg
Kojonazarov, Baktybek
Sydykov, Akylbek
Hirschhäuser, Christine
Wolf, Annemarie
Haag, Daniela
Hecker, Matthias
Fink, Ludger
Seeger, Werner
Ghofrani, Hossein A
Schermuly, Ralph T
Weißmann, Norbert
Schulz, Rainer
Rohrbach, Susanne
Li, Ling
Sommer, Natascha
Schlüter, Klaus-Dieter
author_sort Esfandiary, Azadeh
collection PubMed
description AIMS: The role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2(−/−)) protected against cardiac hypertrophy and failure. However, in UCP2(−/−) mice increased proliferation of pulmonary arterial smooth muscle cells induces mild pulmonary hypertension, right ventricular (RV) hypertrophy, and reduced cardiac output. This suggests a different role for UCP2 in RV and left ventricular adaptation to pressure overload. To clarify this situation in more detail UCP2(−/−) and wild-type mice were exposed to pulmonary arterial banding (PAB). METHODS AND RESULTS: Mice were analysed (haemodynamics, morphometry, and echocardiography) 3 weeks after PAB or sham surgery. Myocytes and non-myocytes were isolated and analysed separately. Cell shortening of myocytes and fura-2 loading of cardiomyocytes were used to characterize their function. Brd assay was performed to study fibroblast proliferation. Isolated mitochondria were analysed to investigate the role of UCP2 for reactive oxygen species (ROS) production. UCP2 mRNA was 2.7-fold stronger expressed in RV myocytes than in left ventricular myocytes and stronger expressed in non-myocytes compared with myocytes. Three weeks after PAB, cardiac output was reduced in wild type but preserved in UCP2(−/−) mice. UCP2(−/−) had increased RV wall thickness, but lower RV internal diameters and displayed a significant stronger fibrosis. Cardiac fibroblasts from UCP2(−/−) had reduced proliferation rates but higher collagen-1 expression. Myocytes isolated from mice after PAB banding showed preserved function that was further improved by UCP2(−/−). Mitochondrial ROS production and respiration was similar between UCP2(−/−) or wild-type hearts. CONCLUSION: Despite a mild pulmonary hypertension in UCP2(−/−) mice, hearts from these mice are well preserved against additional pressure overload (severe pulmonary hypertension). This—at least in part—depends on different behaviour of non-myocytes (fibroblasts).
format Online
Article
Text
id pubmed-6529920
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-65299202019-05-28 Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing Esfandiary, Azadeh Kutsche, Hanna S Schreckenberg, Rolf Weber, Martin Pak, Oleg Kojonazarov, Baktybek Sydykov, Akylbek Hirschhäuser, Christine Wolf, Annemarie Haag, Daniela Hecker, Matthias Fink, Ludger Seeger, Werner Ghofrani, Hossein A Schermuly, Ralph T Weißmann, Norbert Schulz, Rainer Rohrbach, Susanne Li, Ling Sommer, Natascha Schlüter, Klaus-Dieter Cardiovasc Res Spotlight Original Articles AIMS: The role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2(−/−)) protected against cardiac hypertrophy and failure. However, in UCP2(−/−) mice increased proliferation of pulmonary arterial smooth muscle cells induces mild pulmonary hypertension, right ventricular (RV) hypertrophy, and reduced cardiac output. This suggests a different role for UCP2 in RV and left ventricular adaptation to pressure overload. To clarify this situation in more detail UCP2(−/−) and wild-type mice were exposed to pulmonary arterial banding (PAB). METHODS AND RESULTS: Mice were analysed (haemodynamics, morphometry, and echocardiography) 3 weeks after PAB or sham surgery. Myocytes and non-myocytes were isolated and analysed separately. Cell shortening of myocytes and fura-2 loading of cardiomyocytes were used to characterize their function. Brd assay was performed to study fibroblast proliferation. Isolated mitochondria were analysed to investigate the role of UCP2 for reactive oxygen species (ROS) production. UCP2 mRNA was 2.7-fold stronger expressed in RV myocytes than in left ventricular myocytes and stronger expressed in non-myocytes compared with myocytes. Three weeks after PAB, cardiac output was reduced in wild type but preserved in UCP2(−/−) mice. UCP2(−/−) had increased RV wall thickness, but lower RV internal diameters and displayed a significant stronger fibrosis. Cardiac fibroblasts from UCP2(−/−) had reduced proliferation rates but higher collagen-1 expression. Myocytes isolated from mice after PAB banding showed preserved function that was further improved by UCP2(−/−). Mitochondrial ROS production and respiration was similar between UCP2(−/−) or wild-type hearts. CONCLUSION: Despite a mild pulmonary hypertension in UCP2(−/−) mice, hearts from these mice are well preserved against additional pressure overload (severe pulmonary hypertension). This—at least in part—depends on different behaviour of non-myocytes (fibroblasts). Oxford University Press 2019-06-01 2019-03-08 /pmc/articles/PMC6529920/ /pubmed/30850841 http://dx.doi.org/10.1093/cvr/cvz049 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Spotlight Original Articles
Esfandiary, Azadeh
Kutsche, Hanna S
Schreckenberg, Rolf
Weber, Martin
Pak, Oleg
Kojonazarov, Baktybek
Sydykov, Akylbek
Hirschhäuser, Christine
Wolf, Annemarie
Haag, Daniela
Hecker, Matthias
Fink, Ludger
Seeger, Werner
Ghofrani, Hossein A
Schermuly, Ralph T
Weißmann, Norbert
Schulz, Rainer
Rohrbach, Susanne
Li, Ling
Sommer, Natascha
Schlüter, Klaus-Dieter
Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title_full Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title_fullStr Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title_full_unstemmed Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title_short Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
title_sort protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
topic Spotlight Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529920/
https://www.ncbi.nlm.nih.gov/pubmed/30850841
http://dx.doi.org/10.1093/cvr/cvz049
work_keys_str_mv AT esfandiaryazadeh protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT kutschehannas protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT schreckenbergrolf protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT webermartin protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT pakoleg protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT kojonazarovbaktybek protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT sydykovakylbek protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT hirschhauserchristine protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT wolfannemarie protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT haagdaniela protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT heckermatthias protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT finkludger protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT seegerwerner protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT ghofranihosseina protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT schermulyralpht protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT weißmannnorbert protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT schulzrainer protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT rohrbachsusanne protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT liling protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT sommernatascha protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing
AT schluterklausdieter protectionagainstpressureoverloadinducedrightheartfailurebyuncouplingprotein2silencing