Effects of Intermittent Normoxia on Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats

Xu, Chi; Guo, Guijie; Xu, Xiang; Li, Xin; Wei, Qingxia; Shen, Yanying; Li, Hanlu; Hao, Jianxiu; Tian, Ya; He, Kunlun

doi:10.1089/ham.2020.0110

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…We have shown in animal models that intermittent short-duration reoxygenation, which reaches the physiological equivalent height of sea level three times per day for one hour at a time, can effectively reduce pulmonary hypertension and right heart hypertrophy caused by chronic hypoxia, but the mechanism is not completely clear [6] . In addition, other researchers have reached similar conclusions [7] .…”

Section: Introductionsupporting

confidence: 69%

The NLRP3 inflammasome in alveolar macrophages promotes angiogenesis in intermittent short-duration reoxygenation which relieves chronic hypoxic pulmonary hypertension

Cai

Shi

et al. 2023

Preprint

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High altitude pulmonary hypertension (HAPH) is a chronic progressive disease caused by the reconstruction of distal pulmonary arterioles caused by chronic hypoxia. Due to the limited effect of current protective measures for treating HAPH, we propose the use of intermittent short-duration reoxygenation and prove its effectiveness in protecting against HAPH in an animal model. However, the mechanism of relieving HAPH by intermittent short-duration reoxygenation still needs to be further clarified. Previous studies have shown that alveolar macrophages and the inflammatory response induced by the NLRP3 inflammasome play an important role in the development of hypoxic pulmonary hypertension. However, repeated hypoxia and reoxygenation may lead to increased levels of inflammation due to increased oxidative stress. Therefore, the purpose of this study was to examine the changes in alveolar macrophages and the NLRP3 inflammasome under intermittent short-duration reoxygenation and their role in the protective effect. The results showed that intermittent short-duration reoxygenation resulted in higher density of pulmonary vessel bed and higher expression of the NLRP3 inflammasome in lung tissues and alveolar macrophages than continuous hypoxia. In addition, the depletion of alveolar macrophages or inhibition of the NLRP3 inflammasome in the lung counteracted the protective effect of intermittent short-duration reoxygenation on HAPH. Based on these results, we suggest that alveolar macrophages and the NLRP3 inflammasome promote angiogenesis in intermittent short-duration reoxygenation-mediated protection against HAPH.

show abstract

Section: Introductionsupporting

confidence: 69%

The NLRP3 inflammasome in alveolar macrophages promotes angiogenesis in intermittent short-duration reoxygenation which relieves chronic hypoxic pulmonary hypertension

Cai

Shi

et al. 2023

Preprint

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show abstract

“…It is believed that hypoxia-induced diseases can be prevented by treating hypoxia directly. Studies have shown that intermittent short-duration reoxygenation can effectively alleviate pulmonary hypertension and right ventricular hypertrophy (RVH) induced by chronic hypoxia [ 2 ], and simulating oxygen supply by descending altitude achieved similar results as oxygen supply at high altitude in rats [ 3 ]. Furthermore, oxygen supply is currently an available countermeasure to high-altitude hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-γ axis

Li,

Lyu,

Shi

et al. 2024

Clinical Science

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High-altitude pulmonary hypertension (HAPH) is a severe and progressive disease that can lead to right heart failure. Intermittent short-duration reoxygenation at high altitude is effective in alleviating HAPH; however, the underlying mechanisms are unclear. In this study, a simulated 5,000-m hypoxia rat model and hypoxic cultured pulmonary artery smooth muscle cells (PASMCs) were used to evaluate the effect and mechanisms of intermittent short-duration reoxygenation. The results showed that intermittent 3-hour/per day reoxygenation (I3) effectively attenuated chronic hypoxia-induced pulmonary hypertension and reduced the content of H2O2 and the expression of NADPH oxidase 4 (NOX4) in lung tissues. In combination with I3, while the NOX inhibitor apocynin did not further alleviate HAPH, the mitochondrial antioxidant MitoQ did. Furthermore, in PASMCs, I3 attenuated hypoxia-induced PASMCs proliferation and reversed the activated HIF-1α/NOX4/PPAR-γ axis under hypoxia. Targeting this axis offset the protective effect of I3 on hypoxia-induced PASMCs proliferation. This study is novel in revealing a new mechanism for preventing HAPH and provides insights into the optimization of intermittent short-duration reoxygenation.

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Kallikrein-related peptidase-8 (KLK8) aggravated hypoxia-induced right ventricular hypertrophy by targeting P38 MAPK/P53 signaling pathway

Sun¹,

Li²,

Wang³

et al. 2022

Tissue and Cell

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Effects of Intermittent Normoxia on Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Rats

Cited by 5 publications

References 21 publications

The NLRP3 inflammasome in alveolar macrophages promotes angiogenesis in intermittent short-duration reoxygenation which relieves chronic hypoxic pulmonary hypertension

The NLRP3 inflammasome in alveolar macrophages promotes angiogenesis in intermittent short-duration reoxygenation which relieves chronic hypoxic pulmonary hypertension

Intermittent short-duration reoxygenation relieves high-altitude pulmonary hypertension via NOX4/H2O2/PPAR-γ axis

Kallikrein-related peptidase-8 (KLK8) aggravated hypoxia-induced right ventricular hypertrophy by targeting P38 MAPK/P53 signaling pathway

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