Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications
Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmo...
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Taylor & Francis Group
2025-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2025.2500383 |
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| author | Dengfeng Wu Jiangbiao Xiong Yiping Huang Yue Yuan Shunjia Xing Rui Wu |
| author_facet | Dengfeng Wu Jiangbiao Xiong Yiping Huang Yue Yuan Shunjia Xing Rui Wu |
| author_sort | Dengfeng Wu |
| collection | DOAJ |
| description | Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (p < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH. |
| format | Article |
| id | doaj-art-b03cee13e7ab41dd9bec913ba0394074 |
| institution | OA Journals |
| issn | 1064-1963 1525-6006 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
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| series | Clinical and Experimental Hypertension |
| spelling | doaj-art-b03cee13e7ab41dd9bec913ba03940742025-08-20T02:12:53ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062025-12-0147110.1080/10641963.2025.2500383Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verificationsDengfeng Wu0Jiangbiao Xiong1Yiping Huang2Yue Yuan3Shunjia Xing4Rui Wu5Department of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Rheumatology and Immunology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaPulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (p < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH.https://www.tandfonline.com/doi/10.1080/10641963.2025.2500383Pulmonary arterial hypertensionsystemic lupus erythematosusanimal modelhypoxiaMRL/lpr mice |
| spellingShingle | Dengfeng Wu Jiangbiao Xiong Yiping Huang Yue Yuan Shunjia Xing Rui Wu Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications Clinical and Experimental Hypertension Pulmonary arterial hypertension systemic lupus erythematosus animal model hypoxia MRL/lpr mice |
| title | Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications |
| title_full | Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications |
| title_fullStr | Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications |
| title_full_unstemmed | Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications |
| title_short | Establishment of a lupus-prone mouse model of pulmonary arterial hypertension with intermittent hypoxia: functional, biochemical and histological verifications |
| title_sort | establishment of a lupus prone mouse model of pulmonary arterial hypertension with intermittent hypoxia functional biochemical and histological verifications |
| topic | Pulmonary arterial hypertension systemic lupus erythematosus animal model hypoxia MRL/lpr mice |
| url | https://www.tandfonline.com/doi/10.1080/10641963.2025.2500383 |
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