Role of TRPC3 in right ventricular dilatation under chronic intermittent hypoxia in 129/SvEv mice
Abstract: 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 potent...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
MDPI
2023
|
| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/17375 |
| Aporte de: |
| id |
I33-R139-123456789-17375 |
|---|---|
| record_format |
dspace |
| spelling |
I33-R139-123456789-173752023-11-23T18:11:58Z Role of TRPC3 in right ventricular dilatation under chronic intermittent hypoxia in 129/SvEv mice Park, Do Yang Heo, Woon Kang, Miran Ahn, Taeyoung Kim, DoHyeon Choi, Ayeon Birnbaumer, Lutz Cho, Hyung Ju Kim, Joo Young APNEA OBSTRUCTIVA DEL SUEÑO HIPOXIA CRONICA INTERMITENTE POTENCIAL RECEPTOR TRANSITORIO CANAL CATIONICO 3 VENTRICULO DERECHO HIPERTROFIA DEL VENTRICULO DERECHO DILATACION DEL VENTRICULO DERECHO ENDOTELINA Abstract: 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. 2023-10-31T11:37:14Z 2023-10-31T11:37:14Z 2023 Artículo Park, D. Y. et al. Role of TRPC3 in right ventricular dilatation under chronic intermittent hypoxia in 129/SvEv mice [en línea]. International Journal of Molecular Sciences. 2023, 24(14), 11284. doi: 10.3390/ijms241411284. Disponible en: https://repositorio.uca.edu.ar/handle/123456789/17375 1422-0067 https://repositorio.uca.edu.ar/handle/123456789/17375 10.3390/ijms241411284 37511045 eng Acceso abierto http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf MDPI International Journal of Molecular Sciences. Vol. 24, No.14, 11284, 2023 |
| institution |
Universidad Católica Argentina |
| institution_str |
I-33 |
| repository_str |
R-139 |
| collection |
Repositorio Institucional de la Universidad Católica Argentina (UCA) |
| language |
Inglés |
| topic |
APNEA OBSTRUCTIVA DEL SUEÑO HIPOXIA CRONICA INTERMITENTE POTENCIAL RECEPTOR TRANSITORIO CANAL CATIONICO 3 VENTRICULO DERECHO HIPERTROFIA DEL VENTRICULO DERECHO DILATACION DEL VENTRICULO DERECHO ENDOTELINA |
| spellingShingle |
APNEA OBSTRUCTIVA DEL SUEÑO HIPOXIA CRONICA INTERMITENTE POTENCIAL RECEPTOR TRANSITORIO CANAL CATIONICO 3 VENTRICULO DERECHO HIPERTROFIA DEL VENTRICULO DERECHO DILATACION DEL VENTRICULO DERECHO ENDOTELINA Park, Do Yang Heo, Woon Kang, Miran Ahn, Taeyoung Kim, DoHyeon Choi, Ayeon Birnbaumer, Lutz Cho, Hyung Ju Kim, Joo Young Role of TRPC3 in right ventricular dilatation under chronic intermittent hypoxia in 129/SvEv mice |
| topic_facet |
APNEA OBSTRUCTIVA DEL SUEÑO HIPOXIA CRONICA INTERMITENTE POTENCIAL RECEPTOR TRANSITORIO CANAL CATIONICO 3 VENTRICULO DERECHO HIPERTROFIA DEL VENTRICULO DERECHO DILATACION DEL VENTRICULO DERECHO ENDOTELINA |
| description |
Abstract: 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. |
| format |
Artículo |
| author |
Park, Do Yang Heo, Woon Kang, Miran Ahn, Taeyoung Kim, DoHyeon Choi, Ayeon Birnbaumer, Lutz Cho, Hyung Ju Kim, Joo Young |
| author_facet |
Park, Do Yang Heo, Woon Kang, Miran Ahn, Taeyoung Kim, DoHyeon Choi, Ayeon Birnbaumer, Lutz Cho, Hyung Ju Kim, Joo Young |
| author_sort |
Park, Do Yang |
| title |
Role of TRPC3 in right ventricular dilatation under chronic intermittent hypoxia in 129/SvEv mice |
| 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 |
| publisher |
MDPI |
| publishDate |
2023 |
| url |
https://repositorio.uca.edu.ar/handle/123456789/17375 |
| work_keys_str_mv |
AT parkdoyang roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT heowoon roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT kangmiran roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT ahntaeyoung roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT kimdohyeon roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT choiayeon roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT birnbaumerlutz roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT chohyungju roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice AT kimjooyoung roleoftrpc3inrightventriculardilatationunderchronicintermittenthypoxiain129svevmice |
| _version_ |
1807949342793793536 |