Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice

Autores
Malkmus, Kathrin; Brosien, Monika; Knoepp, Fenja; Schaffelhofer, Lisa; Grimminger, Friedrich; Rummel, Christoph; Gudermann, Thomas; Dietrich, Alexander; Birnbaumer, Lutz; Weissmann, Norbert; Kraut, Simone
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic hypoxia-induced pulmonary hypertension (CHPH) is a severe disease that is characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) leading to pulmonary vascular remodeling. The resulting increase in pulmonary vascular resistance (PVR) causes right ventricular hypertrophy and ultimately right heart failure. In addition, increased PVR can also be a consequence of hypoxic pulmonary vasoconstriction (HPV) under generalized hypoxia. Increased proliferation and migration of PASMCs are often associated with high intracellular Ca2+ concentration. Recent publications suggest that Ca2+-permeable nonselective classical transient receptor potential (TRPC) proteins—especially TRPC1 and 6—are crucially involved in acute and sustained hypoxic responses and the pathogenesis of CHPH. The aim of our study was to investigate whether the simultaneous deletion of TRPC proteins 1, 3 and 6 protects against CHPH-development and affects HPV in mice. We used a mouse model of chronic hypoxia as well as isolated, ventilated and perfused mouse lungs and PASMC cell cultures. Although right ventricular systolic pressure as well as echocardiographically assessed PVR and right ventricular wall thickness (RVWT) were lower in TRPC1, 3, 6-deficient mice, these changes were not related to a decreased degree of pulmonary vascular muscularization and a reduced proliferation of PASMCs. However, both acute and sustained HPV were almost absent in the TRPC1, 3, 6-deficient mice and their vasoconstrictor response upon KCl application was reduced. This was further validated by myographical experiments. Our data revealed that 1) TRPC1, 3, 6-deficient mice are partially protected against development of CHPH, 2) these changes may be caused by diminished HPV and not an altered pulmonary vascular remodeling.
Fil: Malkmus, Kathrin. Justus Liebig Universitat Giessen; Alemania
Fil: Brosien, Monika. Justus Liebig Universitat Giessen; Alemania
Fil: Knoepp, Fenja. Justus Liebig Universitat Giessen; Alemania
Fil: Schaffelhofer, Lisa. Justus Liebig Universitat Giessen; Alemania
Fil: Grimminger, Friedrich. Justus Liebig Universitat Giessen; Alemania
Fil: Rummel, Christoph. Justus Liebig Universitat Giessen; Alemania
Fil: Gudermann, Thomas. Ludwig Maximilians Universitat; Alemania
Fil: Dietrich, Alexander. Ludwig Maximilians Universitat; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Weissmann, Norbert. Ludwig Maximilians Universitat; Alemania
Fil: Kraut, Simone. Ludwig Maximilians Universitat; Alemania
Materia
CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION
MICE
PROLIFERATION
PULMONARY ARTERIAL SMOOTH MUSCLE CELLS (PASMCS)
PULMONARY HYPOXIC VASOCONSTRICTION
PULMONARY VASCULAR REMODELING
TRPC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/217857
Acceder
id CONICETDig_ad3cff9ba0e4d2bd5632c539a11c47a1
oai_identifier_str oai:ri.conicet.gov.ar:11336/217857
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in miceMalkmus, KathrinBrosien, MonikaKnoepp, FenjaSchaffelhofer, LisaGrimminger, FriedrichRummel, ChristophGudermann, ThomasDietrich, AlexanderBirnbaumer, LutzWeissmann, NorbertKraut, SimoneCHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSIONMICEPROLIFERATIONPULMONARY ARTERIAL SMOOTH MUSCLE CELLS (PASMCS)PULMONARY HYPOXIC VASOCONSTRICTIONPULMONARY VASCULAR REMODELINGTRPChttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chronic hypoxia-induced pulmonary hypertension (CHPH) is a severe disease that is characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) leading to pulmonary vascular remodeling. The resulting increase in pulmonary vascular resistance (PVR) causes right ventricular hypertrophy and ultimately right heart failure. In addition, increased PVR can also be a consequence of hypoxic pulmonary vasoconstriction (HPV) under generalized hypoxia. Increased proliferation and migration of PASMCs are often associated with high intracellular Ca2+ concentration. Recent publications suggest that Ca2+-permeable nonselective classical transient receptor potential (TRPC) proteins—especially TRPC1 and 6—are crucially involved in acute and sustained hypoxic responses and the pathogenesis of CHPH. The aim of our study was to investigate whether the simultaneous deletion of TRPC proteins 1, 3 and 6 protects against CHPH-development and affects HPV in mice. We used a mouse model of chronic hypoxia as well as isolated, ventilated and perfused mouse lungs and PASMC cell cultures. Although right ventricular systolic pressure as well as echocardiographically assessed PVR and right ventricular wall thickness (RVWT) were lower in TRPC1, 3, 6-deficient mice, these changes were not related to a decreased degree of pulmonary vascular muscularization and a reduced proliferation of PASMCs. However, both acute and sustained HPV were almost absent in the TRPC1, 3, 6-deficient mice and their vasoconstrictor response upon KCl application was reduced. This was further validated by myographical experiments. Our data revealed that 1) TRPC1, 3, 6-deficient mice are partially protected against development of CHPH, 2) these changes may be caused by diminished HPV and not an altered pulmonary vascular remodeling.Fil: Malkmus, Kathrin. Justus Liebig Universitat Giessen; AlemaniaFil: Brosien, Monika. Justus Liebig Universitat Giessen; AlemaniaFil: Knoepp, Fenja. Justus Liebig Universitat Giessen; AlemaniaFil: Schaffelhofer, Lisa. Justus Liebig Universitat Giessen; AlemaniaFil: Grimminger, Friedrich. Justus Liebig Universitat Giessen; AlemaniaFil: Rummel, Christoph. Justus Liebig Universitat Giessen; AlemaniaFil: Gudermann, Thomas. Ludwig Maximilians Universitat; AlemaniaFil: Dietrich, Alexander. Ludwig Maximilians Universitat; AlemaniaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Weissmann, Norbert. Ludwig Maximilians Universitat; AlemaniaFil: Kraut, Simone. Ludwig Maximilians Universitat; AlemaniaFrontiers Media2022-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/217857Malkmus, Kathrin; Brosien, Monika; Knoepp, Fenja; Schaffelhofer, Lisa; Grimminger, Friedrich; et al.; Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice; Frontiers Media; Frontiers in Physiology; 13; 12-2022; 1-151664-042XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fphys.2022.1080875info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:00:26Zoai:ri.conicet.gov.ar:11336/217857instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:00:27.113CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
title Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
spellingShingle Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
Malkmus, Kathrin
CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION
MICE
PROLIFERATION
PULMONARY ARTERIAL SMOOTH MUSCLE CELLS (PASMCS)
PULMONARY HYPOXIC VASOCONSTRICTION
PULMONARY VASCULAR REMODELING
TRPC
title_short Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
title_full Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
title_fullStr Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
title_full_unstemmed Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
title_sort Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice
dc.creator.none.fl_str_mv Malkmus, Kathrin
Brosien, Monika
Knoepp, Fenja
Schaffelhofer, Lisa
Grimminger, Friedrich
Rummel, Christoph
Gudermann, Thomas
Dietrich, Alexander
Birnbaumer, Lutz
Weissmann, Norbert
Kraut, Simone
author Malkmus, Kathrin
author_facet Malkmus, Kathrin
Brosien, Monika
Knoepp, Fenja
Schaffelhofer, Lisa
Grimminger, Friedrich
Rummel, Christoph
Gudermann, Thomas
Dietrich, Alexander
Birnbaumer, Lutz
Weissmann, Norbert
Kraut, Simone
author_role author
author2 Brosien, Monika
Knoepp, Fenja
Schaffelhofer, Lisa
Grimminger, Friedrich
Rummel, Christoph
Gudermann, Thomas
Dietrich, Alexander
Birnbaumer, Lutz
Weissmann, Norbert
Kraut, Simone
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION
MICE
PROLIFERATION
PULMONARY ARTERIAL SMOOTH MUSCLE CELLS (PASMCS)
PULMONARY HYPOXIC VASOCONSTRICTION
PULMONARY VASCULAR REMODELING
TRPC
topic CHRONIC HYPOXIA-INDUCED PULMONARY HYPERTENSION
MICE
PROLIFERATION
PULMONARY ARTERIAL SMOOTH MUSCLE CELLS (PASMCS)
PULMONARY HYPOXIC VASOCONSTRICTION
PULMONARY VASCULAR REMODELING
TRPC
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chronic hypoxia-induced pulmonary hypertension (CHPH) is a severe disease that is characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) leading to pulmonary vascular remodeling. The resulting increase in pulmonary vascular resistance (PVR) causes right ventricular hypertrophy and ultimately right heart failure. In addition, increased PVR can also be a consequence of hypoxic pulmonary vasoconstriction (HPV) under generalized hypoxia. Increased proliferation and migration of PASMCs are often associated with high intracellular Ca2+ concentration. Recent publications suggest that Ca2+-permeable nonselective classical transient receptor potential (TRPC) proteins—especially TRPC1 and 6—are crucially involved in acute and sustained hypoxic responses and the pathogenesis of CHPH. The aim of our study was to investigate whether the simultaneous deletion of TRPC proteins 1, 3 and 6 protects against CHPH-development and affects HPV in mice. We used a mouse model of chronic hypoxia as well as isolated, ventilated and perfused mouse lungs and PASMC cell cultures. Although right ventricular systolic pressure as well as echocardiographically assessed PVR and right ventricular wall thickness (RVWT) were lower in TRPC1, 3, 6-deficient mice, these changes were not related to a decreased degree of pulmonary vascular muscularization and a reduced proliferation of PASMCs. However, both acute and sustained HPV were almost absent in the TRPC1, 3, 6-deficient mice and their vasoconstrictor response upon KCl application was reduced. This was further validated by myographical experiments. Our data revealed that 1) TRPC1, 3, 6-deficient mice are partially protected against development of CHPH, 2) these changes may be caused by diminished HPV and not an altered pulmonary vascular remodeling.
Fil: Malkmus, Kathrin. Justus Liebig Universitat Giessen; Alemania
Fil: Brosien, Monika. Justus Liebig Universitat Giessen; Alemania
Fil: Knoepp, Fenja. Justus Liebig Universitat Giessen; Alemania
Fil: Schaffelhofer, Lisa. Justus Liebig Universitat Giessen; Alemania
Fil: Grimminger, Friedrich. Justus Liebig Universitat Giessen; Alemania
Fil: Rummel, Christoph. Justus Liebig Universitat Giessen; Alemania
Fil: Gudermann, Thomas. Ludwig Maximilians Universitat; Alemania
Fil: Dietrich, Alexander. Ludwig Maximilians Universitat; Alemania
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Weissmann, Norbert. Ludwig Maximilians Universitat; Alemania
Fil: Kraut, Simone. Ludwig Maximilians Universitat; Alemania
description Chronic hypoxia-induced pulmonary hypertension (CHPH) is a severe disease that is characterized by increased proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) leading to pulmonary vascular remodeling. The resulting increase in pulmonary vascular resistance (PVR) causes right ventricular hypertrophy and ultimately right heart failure. In addition, increased PVR can also be a consequence of hypoxic pulmonary vasoconstriction (HPV) under generalized hypoxia. Increased proliferation and migration of PASMCs are often associated with high intracellular Ca2+ concentration. Recent publications suggest that Ca2+-permeable nonselective classical transient receptor potential (TRPC) proteins—especially TRPC1 and 6—are crucially involved in acute and sustained hypoxic responses and the pathogenesis of CHPH. The aim of our study was to investigate whether the simultaneous deletion of TRPC proteins 1, 3 and 6 protects against CHPH-development and affects HPV in mice. We used a mouse model of chronic hypoxia as well as isolated, ventilated and perfused mouse lungs and PASMC cell cultures. Although right ventricular systolic pressure as well as echocardiographically assessed PVR and right ventricular wall thickness (RVWT) were lower in TRPC1, 3, 6-deficient mice, these changes were not related to a decreased degree of pulmonary vascular muscularization and a reduced proliferation of PASMCs. However, both acute and sustained HPV were almost absent in the TRPC1, 3, 6-deficient mice and their vasoconstrictor response upon KCl application was reduced. This was further validated by myographical experiments. Our data revealed that 1) TRPC1, 3, 6-deficient mice are partially protected against development of CHPH, 2) these changes may be caused by diminished HPV and not an altered pulmonary vascular remodeling.
publishDate 2022
dc.date.none.fl_str_mv 2022-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/217857
Malkmus, Kathrin; Brosien, Monika; Knoepp, Fenja; Schaffelhofer, Lisa; Grimminger, Friedrich; et al.; Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice; Frontiers Media; Frontiers in Physiology; 13; 12-2022; 1-15
1664-042X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/217857
identifier_str_mv Malkmus, Kathrin; Brosien, Monika; Knoepp, Fenja; Schaffelhofer, Lisa; Grimminger, Friedrich; et al.; Deletion of classical transient receptor potential 1, 3 and 6 alters pulmonary vasoconstriction in chronic hypoxia-induced pulmonary hypertension in mice; Frontiers Media; Frontiers in Physiology; 13; 12-2022; 1-15
1664-042X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fphys.2022.1080875
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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