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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Main Authors: Shi Haixia, Zhao Yongfeng, Li Su, Wu Haitao, Ma Dehua, Wan Chenchen
Format: Article
Language:English
Published: De Gruyter 2023-07-01
Series:Open Life Sciences
Subjects:
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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