PMID- 38237016
OWN - NLM
STAT- MEDLINE
DCOM- 20240212
LR  - 20240416
IS  - 1470-8736 (Electronic)
IS  - 0143-5221 (Print)
IS  - 0143-5221 (Linking)
VI  - 138
IP  - 3
DP  - 2024 Feb 7
TI  - Intermittent short-duration reoxygenation relieves high-altitude pulmonary 
      hypertension via NOX4/H2O2/PPAR-gamma axis.
PG  - 103-115
LID - 10.1042/CS20231508 [doi]
AB  - 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 the present 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-h/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-1alpha/NOX4/PPAR-gamma axis under hypoxia. Targeting this axis offset the protective 
      effect of I3 on hypoxia-induced PASMCs proliferation. The present study is novel 
      in revealing a new mechanism for preventing HAPH and provides insights into the 
      optimization of intermittent short-duration reoxygenation.
CI  - (c) 2024 The Author(s).
FAU - Li, Shaohua
AU  - Li S
AUID- ORCID: 0009-0003-7412-8787
AD  - Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, 
      China.
FAU - Lyu, Qiang
AU  - Lyu Q
AD  - Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of 
      Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 
      100853, China.
FAU - Shi, Qixin
AU  - Shi Q
AD  - Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, 
      China.
FAU - Bai, Yungang
AU  - Bai Y
AD  - Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, 
      China.
FAU - Ren, Xinling
AU  - Ren X
AD  - Department of Respiratory and Critical Care Medicine, Shenzhen University General 
      Hospital, Shenzhen 518071, China.
FAU - Ma, Jin
AU  - Ma J
AUID- ORCID: 0000-0001-6802-455X
AD  - Department of Aerospace Physiology, Air Force Medical University, Xi'an 710032, 
      China.
LA  - eng
GR  - 82202074/National Natural Science Foundation of China/
GR  - 2018HKTS03/Air Force Medical University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - 0 (PPAR gamma)
RN  - EC 1.6.3.- (Nox4 protein, rat)
RN  - Pulmonary edema of mountaineers
SB  - IM
MH  - Animals
MH  - Rats
MH  - Altitude
MH  - *Altitude Sickness
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Hydrogen Peroxide/metabolism
MH  - *Hypertension, Pulmonary/etiology/prevention & control/metabolism
MH  - Hypoxia/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NADPH Oxidase 4/genetics/metabolism
MH  - PPAR gamma/metabolism
MH  - Pulmonary Artery/metabolism
MH  - Signal Transduction
PMC - PMC10830432
OTO - NOTNLM
OT  - NADHP oxidase 4
OT  - hypobaric hypoxia
OT  - intermittent short-duration reoxygenation
OT  - pulmonary hypertension
COIS- The authors declare that there are no competing interests associated with the 
      manuscript.
EDAT- 2024/01/18 18:42
MHDA- 2024/02/05 06:42
PMCR- 2024/01/30
CRDT- 2024/01/18 14:23
PHST- 2023/11/21 00:00 [received]
PHST- 2024/01/16 00:00 [revised]
PHST- 2024/01/18 00:00 [accepted]
PHST- 2024/02/05 06:42 [medline]
PHST- 2024/01/18 18:42 [pubmed]
PHST- 2024/01/18 14:23 [entrez]
PHST- 2024/01/30 00:00 [pmc-release]
AID - 233977 [pii]
AID - CS20231508 [pii]
AID - 10.1042/CS20231508 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2024 Feb 7;138(3):103-115. doi: 10.1042/CS20231508.