TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching...
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De Gruyter
2023-07-01
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Online Access: | https://doi.org/10.1515/biol-2022-0650 |
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author | Shi Haixia Zhao Yongfeng Li Su Wu Haitao Ma Dehua Wan Chenchen |
author_facet | Shi Haixia Zhao Yongfeng Li Su Wu Haitao Ma Dehua Wan Chenchen |
author_sort | Shi Haixia |
collection | DOAJ |
description | The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity. |
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spelling | doaj.art-04924215a9a24bf7887e50b45f6e61082023-08-01T05:14:32ZengDe GruyterOpen Life Sciences2391-54122023-07-01181622910.1515/biol-2022-0650TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in ratsShi Haixia0Zhao Yongfeng1Li Su2Wu Haitao3Ma Dehua4Wan Chenchen5Department of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaDepartment of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaDepartment of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaDepartment of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaDepartment of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaDepartment of Emergency, Affiliated Hospital of Qinghai University, Xining City, Qinghai Province 810001, ChinaThe expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity.https://doi.org/10.1515/biol-2022-0650pulmonary arterial hypertensiontnf-αmean pulmonary arterial pressurepulmonary vascular remodeling |
spellingShingle | Shi Haixia Zhao Yongfeng Li Su Wu Haitao Ma Dehua Wan Chenchen TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats Open Life Sciences pulmonary arterial hypertension tnf-α mean pulmonary arterial pressure pulmonary vascular remodeling |
title | TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
title_full | TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
title_fullStr | TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
title_full_unstemmed | TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
title_short | TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
title_sort | tnf α and il 8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats |
topic | pulmonary arterial hypertension tnf-α mean pulmonary arterial pressure pulmonary vascular remodeling |
url | https://doi.org/10.1515/biol-2022-0650 |
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