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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | Clinical and Experimental Hypertension |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/10641963.2025.2500383 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 1064-1963 1525-6006 |