PMID- 34805208
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211123
IS  - 2296-858X (Print)
IS  - 2296-858X (Electronic)
IS  - 2296-858X (Linking)
VI  - 8
DP  - 2021
TI  - Novel Targets in a High-Altitude Pulmonary Hypertension Rat Model Based on 
      RNA-seq and Proteomics.
PG  - 742436
LID - 10.3389/fmed.2021.742436 [doi]
LID - 742436
AB  - High-altitude pulmonary hypertension (HAPH) is a complication arising from an 
      inability to acclimatize to high altitude and is associated with high morbidity 
      and mortality. We aimed to analyze the effects of macitentan, selexipag, 
      riociguat, and reoxygenation on HAPH, and to screen possible targets of these 
      treatments for future drug screening. Rats were subjected to hypobaric hypoxia 
      for 35 days to induce HAPH, and treated with vehicle or selexipag, macitentan, 
      riociguat, or with reoxygenation, from days 21 to 35. Selexipag, macitentan, and 
      reoxygenation prevented an increase in mean pulmonary artery pressure and 
      hypoxia-induced right ventricular hypertrophy, compared to the vehicle. Riociguat 
      had little effect. RNA-seq and proteomics revealed strong correlations between 
      responses to the three drugs, which had almost identical effects. GO-enrichment 
      revealed that the differentially expressed genes included those involved in 
      metabolic regulation, transcription, and translation. Various molecular pathways 
      were annotated. Selexipag, macitentan, and reoxygenation ameliorated HAPH. 
      Serpina1, Cryz, and Cmc1 were identified, via multi-omics screening, as key genes 
      involved in HAPH. These findings provide new insights into the targeted drug 
      mechanisms in HAPH.
CI  - Copyright (c) 2021 Xu, Li, Wei, Li, Shen, Guo, Chen, He and Liu.
FAU - Xu, Xiang
AU  - Xu X
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - Li, Hanlu
AU  - Li H
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - Wei, Qingxia
AU  - Wei Q
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - Li, Xin
AU  - Li X
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA 
      General Hospital, Beijing, China.
FAU - Shen, Yanying
AU  - Shen Y
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - Guo, Ge
AU  - Guo G
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - Chen, Yibing
AU  - Chen Y
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
FAU - He, Kunlun
AU  - He K
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA 
      General Hospital, Beijing, China.
FAU - Liu, Chunlei
AU  - Liu C
AD  - Laboratory of Translational Medicine, Medical Innovation Research Division of 
      Chinese PLA General Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, Chinese PLA 
      General Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20211103
PL  - Switzerland
TA  - Front Med (Lausanne)
JT  - Frontiers in medicine
JID - 101648047
PMC - PMC8595261
OTO - NOTNLM
OT  - RNA-seq
OT  - high-altitude pulmonary hypertension
OT  - macitentan
OT  - proteomics
OT  - reoxygenation
OT  - selexipag
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/23 06:00
MHDA- 2021/11/23 06:01
PMCR- 2021/11/03
CRDT- 2021/11/22 06:53
PHST- 2021/07/16 00:00 [received]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/11/22 06:53 [entrez]
PHST- 2021/11/23 06:00 [pubmed]
PHST- 2021/11/23 06:01 [medline]
PHST- 2021/11/03 00:00 [pmc-release]
AID - 10.3389/fmed.2021.742436 [doi]
PST - epublish
SO  - Front Med (Lausanne). 2021 Nov 3;8:742436. doi: 10.3389/fmed.2021.742436. 
      eCollection 2021.