Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice

Autores
Park, Do Yang; Heo, Woon; Kang, Miran; Ahn, Taeyoung; Kim, DoHyeon; Choi, Ayeon; Birnbaumer, Lutz; Cho, Hyung Ju; Kim, Joo Young
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.
Fil: Park, Do Yang. Ajou University School of Medicine; Corea del Sur
Fil: Heo, Woon. Yonsei University College Of Medicine; Corea del Sur
Fil: Kang, Miran. Yonsei University College Of Medicine; Corea del Sur
Fil: Ahn, Taeyoung. Yonsei University College Of Medicine; Corea del Sur
Fil: Kim, DoHyeon. Yonsei University College Of Medicine; Corea del Sur
Fil: Choi, Ayeon. Yonsei University College Of Medicine; Corea del Sur
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: Cho, Hyung Ju. Yonsei University College Of Medicine; Corea del Sur
Fil: Kim, Joo Young. Yonsei University College Of Medicine; Corea del Sur
Materia
right ventricle
obstructive sleep apnea
endothelin
chronic intermittent hypoxia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/255449
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/255449
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv MicePark, Do YangHeo, WoonKang, MiranAhn, TaeyoungKim, DoHyeonChoi, AyeonBirnbaumer, LutzCho, Hyung JuKim, Joo Youngright ventricleobstructive sleep apneaendothelinchronic intermittent hypoxiahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.Fil: Park, Do Yang. Ajou University School of Medicine; Corea del SurFil: Heo, Woon. Yonsei University College Of Medicine; Corea del SurFil: Kang, Miran. Yonsei University College Of Medicine; Corea del SurFil: Ahn, Taeyoung. Yonsei University College Of Medicine; Corea del SurFil: Kim, DoHyeon. Yonsei University College Of Medicine; Corea del SurFil: Choi, Ayeon. Yonsei University College Of Medicine; Corea del SurFil: 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: Cho, Hyung Ju. Yonsei University College Of Medicine; Corea del SurFil: Kim, Joo Young. Yonsei University College Of Medicine; Corea del SurMolecular Diversity Preservation International2023-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/255449Park, Do Yang; Heo, Woon; Kang, Miran; Ahn, Taeyoung; Kim, DoHyeon; et al.; Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 14; 7-2023; 1-131422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/14/11284info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms241411284info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:51:23Zoai:ri.conicet.gov.ar:11336/255449instacron: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:34982025-09-17 10:51:23.602CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
title Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
spellingShingle Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
Park, Do Yang
right ventricle
obstructive sleep apnea
endothelin
chronic intermittent hypoxia
title_short Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
title_full Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
title_fullStr Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
title_full_unstemmed Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
title_sort Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice
dc.creator.none.fl_str_mv Park, Do Yang
Heo, Woon
Kang, Miran
Ahn, Taeyoung
Kim, DoHyeon
Choi, Ayeon
Birnbaumer, Lutz
Cho, Hyung Ju
Kim, Joo Young
author Park, Do Yang
author_facet Park, Do Yang
Heo, Woon
Kang, Miran
Ahn, Taeyoung
Kim, DoHyeon
Choi, Ayeon
Birnbaumer, Lutz
Cho, Hyung Ju
Kim, Joo Young
author_role author
author2 Heo, Woon
Kang, Miran
Ahn, Taeyoung
Kim, DoHyeon
Choi, Ayeon
Birnbaumer, Lutz
Cho, Hyung Ju
Kim, Joo Young
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv right ventricle
obstructive sleep apnea
endothelin
chronic intermittent hypoxia
topic right ventricle
obstructive sleep apnea
endothelin
chronic intermittent hypoxia
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.
Fil: Park, Do Yang. Ajou University School of Medicine; Corea del Sur
Fil: Heo, Woon. Yonsei University College Of Medicine; Corea del Sur
Fil: Kang, Miran. Yonsei University College Of Medicine; Corea del Sur
Fil: Ahn, Taeyoung. Yonsei University College Of Medicine; Corea del Sur
Fil: Kim, DoHyeon. Yonsei University College Of Medicine; Corea del Sur
Fil: Choi, Ayeon. Yonsei University College Of Medicine; Corea del Sur
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: Cho, Hyung Ju. Yonsei University College Of Medicine; Corea del Sur
Fil: Kim, Joo Young. Yonsei University College Of Medicine; Corea del Sur
description Patients with obstructive sleep apnea (OSA) exhibit a high prevalence of pulmonary hypertension and right ventricular (RV) hypertrophy. However, the exact molecule responsible for the pathogenesis remains unknown. Given the resistance to RV dilation observed in transient receptor potential canonical 3(Trpc3)-/- mice during a pulmonary hypertension model induced by phenylephrine (PE), we hypothesized that TRPC3 also plays a role in chronic intermittent hypoxia (CIH) conditions, which lead to RV dilation and dysfunction. To test this, we established an OSA mouse model using 8- to 12-week-old 129/SvEv wild-type and Trpc3-/- mice in a customized breeding chamber that simulated sleep and oxygen cycles. Functional parameters of the RV were evaluated through analysis of cardiac cine magnetic resonance images, while histopathological examinations were conducted on cardiomyocytes and pulmonary vessels. Following exposure to 4 weeks of CIH, Trpc3-/- mice exhibited significant RV dysfunction, characterized by decreased ejection fraction, increased end-diastole RV wall thickness, and elevated expression of pathological cardiac markers. In addition, reactive oxygen species (ROS) signaling and the endothelin system were markedly increased solely in the hearts of CIH-exposed Trpc3-/- mice. Notably, no significant differences in pulmonary vessel thickness or the endothelin system were observed in the lungs of wild-type (WT) and Trpc3-/- mice subjected to 4 weeks of CIH. In conclusion, our findings suggest that TRPC3 serves as a regulator of RV resistance in response to pressure from the pulmonary vasculature, as evidenced by the high susceptibility to RV dilation in Trpc3-/- mice without notable changes in pulmonary vasculature under CIH conditions.
publishDate 2023
dc.date.none.fl_str_mv 2023-07
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/11336/255449
Park, Do Yang; Heo, Woon; Kang, Miran; Ahn, Taeyoung; Kim, DoHyeon; et al.; Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 14; 7-2023; 1-13
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/255449
identifier_str_mv Park, Do Yang; Heo, Woon; Kang, Miran; Ahn, Taeyoung; Kim, DoHyeon; et al.; Role of TRPC3 in Right Ventricular Dilatation under Chronic Intermittent Hypoxia in 129/SvEv Mice; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 24; 14; 7-2023; 1-13
1422-0067
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/24/14/11284
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms241411284
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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 13.001348

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