Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?

OBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac t...

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Autores: Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91, Varo-Cenarruzabeitia, N. (Nerea)|||/items/18b5a757-44b9-4e23-8a8c-ad907969001f, Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41, Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Tipo de recurso: artículo
Fecha de publicación:2007
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/21860
Acceso en línea:https://hdl.handle.net/10171/21860
Access Level:acceso abierto
Palabra clave:Cardiomyocytes
Cardiotrophin-1
Heart failure
Hypertension
LIF receptor
SHR
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spelling Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91Varo-Cenarruzabeitia, N. (Nerea)|||/items/18b5a757-44b9-4e23-8a8c-ad907969001fDiez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ecCardiomyocytesCardiotrophin-1Heart failureHypertensionLIF receptorSHROBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac tissue and in cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH (non-failing SHR) and from aged SHR with overt HF (failing SHR). METHODS: Cardiac morphometry was assayed by planimetry in an image analysis system. mRNA and protein expression were quantified by real time RT-PCR and Western blotting. Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and MTT cell viability assays were employed to study the cytoprotective activity of cardiotrophin-1 (CT-1) in isolated caridomyocytes. RESULTS: Compared to non-failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01) demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non-failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent in cardiomyocytes isolated from failing SHR, which were resistant to the cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<0.01) LIFR expression. CONCLUSIONS: These data suggest that loss of CT-1-dependent survival mechanisms may contribute to the increase of cell death associated with HF in SHR. Neurohumoral activation may contribute to this alteration via suppression of LIFR.Oxford University PressDadun. Depósito Académico Digital Universidad de Navarra20122012-05-0220072007-01-0120072007-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfapplication/pdfhttps://hdl.handle.net/10171/21860reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/218602026-06-21T12:47:57Z
dc.title.none.fl_str_mv Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
title Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
spellingShingle Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91
Cardiomyocytes
Cardiotrophin-1
Heart failure
Hypertension
LIF receptor
SHR
title_short Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
title_full Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
title_fullStr Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
title_full_unstemmed Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
title_sort Loss of myocardial LIF receptor in experimental heart failure reduces cardiotrophin-1 cytoprotection. A role for neurohumoral agonists?
dc.creator.none.fl_str_mv Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91
Varo-Cenarruzabeitia, N. (Nerea)|||/items/18b5a757-44b9-4e23-8a8c-ad907969001f
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
author Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91
author_facet Lopez, N. (Natalia)|||/items/0edf59fe-771c-4a1c-98bf-cd0d8dd4cb91
Varo-Cenarruzabeitia, N. (Nerea)|||/items/18b5a757-44b9-4e23-8a8c-ad907969001f
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
author_role author
author2 Varo-Cenarruzabeitia, N. (Nerea)|||/items/18b5a757-44b9-4e23-8a8c-ad907969001f
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
author2_role author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Cardiomyocytes
Cardiotrophin-1
Heart failure
Hypertension
LIF receptor
SHR
topic Cardiomyocytes
Cardiotrophin-1
Heart failure
Hypertension
LIF receptor
SHR
description OBJECTIVES: Cardiomyocyte loss is involved in the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Our aim was to investigate the status of the leukaemia inhibitory factor receptor (LIFR)/gp130 survival pathway and its cytoprotective activity in intact cardiac tissue and in cardiomyocytes obtained from adult spontaneously hypertensive rats (SHR) with LVH (non-failing SHR) and from aged SHR with overt HF (failing SHR). METHODS: Cardiac morphometry was assayed by planimetry in an image analysis system. mRNA and protein expression were quantified by real time RT-PCR and Western blotting. Receptors were localized by immunocytochemistry. Trypan blue staining, TUNEL, and MTT cell viability assays were employed to study the cytoprotective activity of cardiotrophin-1 (CT-1) in isolated caridomyocytes. RESULTS: Compared to non-failing SHR, failing SHR exhibited enhanced myocardial cell death (p<0.01) demonstrated by the increase in Bax/Bcl-2 ratio, caspase-3 activation and poly (ADP-ribose) polymerase (PARP) fragmentation. Failing SHR had a 7-fold diminished expression (p<0.01) of LIFR, no changes in gp130, and 1.6-fold increased myocardial expression (p<0.01) of CT-1. In cardiomyocytes isolated from non-failing SHR, recombinant CT-1 inhibited apoptotic and non-apoptotic cell death induced by angiotensin II or hydrogen peroxide. LIFR protein was entirely absent in cardiomyocytes isolated from failing SHR, which were resistant to the cytoprotective effects of CT-1. Finally, stimulation of non-failing SHR cardiomyocytes with angiotensin II, aldosterone, norepinephrine or endothelin-1 significantly decreased (p<0.01) LIFR expression. CONCLUSIONS: These data suggest that loss of CT-1-dependent survival mechanisms may contribute to the increase of cell death associated with HF in SHR. Neurohumoral activation may contribute to this alteration via suppression of LIFR.
publishDate 2007
dc.date.none.fl_str_mv 2007
2007-01-01
2007
2007-01-01
2012
2012-05-02
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/21860
url https://hdl.handle.net/10171/21860
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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