Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies
Abstract Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double‐hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery liga...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Experimental Physiology |
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| Online Access: | https://doi.org/10.1113/EP091833 |
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| author | Lingdan Chen Xin Chen Yuhang Huang Zhuoji Ma Xiaohui Zeng Tao Wang |
| author_facet | Lingdan Chen Xin Chen Yuhang Huang Zhuoji Ma Xiaohui Zeng Tao Wang |
| author_sort | Lingdan Chen |
| collection | DOAJ |
| description | Abstract Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double‐hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery ligation (LPAL) with hypoxia exposure in C57BL/6 mice. Our detailed haemodynamic and histological evaluations post‐surgery demonstrated pronounced elevations in right ventricular systolic pressure (RVSP) (LPAL: 41.1 ± 4.63 mmHg, P = 0.005; LPx: 38.4 ± 2.95 mmHg, P = 0.002; Sham: 32.1 ± 2.21 mmHg) and pulmonary vascular wall thickness (LPAL: 56.9 ± 3.34%, P = 0.02; LPx: 54.3 ± 4.65%, P = 0.04; Sham: 44.8 ± 3.76%) compared to hypoxia‐exposed sham‐operated controls, reflecting a more severe PH phenotype. These novel models, which exhibit haemodynamic alterations akin to the established hypoxia with SU5416‐induced PH model as per published data, could offer a substantial contribution to future PH research and therapeutic development. |
| format | Article |
| id | doaj-art-1ca43c5b3fdd4f109c665b494a33d190 |
| institution | DOAJ |
| issn | 0958-0670 1469-445X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Experimental Physiology |
| spelling | doaj-art-1ca43c5b3fdd4f109c665b494a33d1902025-08-20T02:48:42ZengWileyExperimental Physiology0958-06701469-445X2024-12-01109122026203010.1113/EP091833Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategiesLingdan Chen0Xin Chen1Yuhang Huang2Zhuoji Ma3Xiaohui Zeng4Tao Wang5State Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Respiratory Medicine, Zhujiang Hosptial Southern Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Diseases, Guangdong Key Laboratory of Vascular Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health the First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong ChinaAbstract Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double‐hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery ligation (LPAL) with hypoxia exposure in C57BL/6 mice. Our detailed haemodynamic and histological evaluations post‐surgery demonstrated pronounced elevations in right ventricular systolic pressure (RVSP) (LPAL: 41.1 ± 4.63 mmHg, P = 0.005; LPx: 38.4 ± 2.95 mmHg, P = 0.002; Sham: 32.1 ± 2.21 mmHg) and pulmonary vascular wall thickness (LPAL: 56.9 ± 3.34%, P = 0.02; LPx: 54.3 ± 4.65%, P = 0.04; Sham: 44.8 ± 3.76%) compared to hypoxia‐exposed sham‐operated controls, reflecting a more severe PH phenotype. These novel models, which exhibit haemodynamic alterations akin to the established hypoxia with SU5416‐induced PH model as per published data, could offer a substantial contribution to future PH research and therapeutic development.https://doi.org/10.1113/EP091833hypoxiamouse modelpneumonectomypulmonary artery ligationpulmonary hypertension |
| spellingShingle | Lingdan Chen Xin Chen Yuhang Huang Zhuoji Ma Xiaohui Zeng Tao Wang Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies Experimental Physiology hypoxia mouse model pneumonectomy pulmonary artery ligation pulmonary hypertension |
| title | Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies |
| title_full | Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies |
| title_fullStr | Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies |
| title_full_unstemmed | Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies |
| title_short | Establishment of mouse models for severe pulmonary hypertension through ‘double‐hit’ strategies |
| title_sort | establishment of mouse models for severe pulmonary hypertension through double hit strategies |
| topic | hypoxia mouse model pneumonectomy pulmonary artery ligation pulmonary hypertension |
| url | https://doi.org/10.1113/EP091833 |
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