PMID- 37586455
OWN - NLM
STAT- MEDLINE
DCOM- 20230920
LR  - 20230920
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 431
IP  - 2
DP  - 2023 Oct 15
TI  - NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension development via 
      IKK/NF-kappaB p65/HIF-1alpha pathway.
PG  - 113755
LID - S0014-4827(23)00303-8 [pii]
LID - 10.1016/j.yexcr.2023.113755 [doi]
AB  - Hypoxia-induced pulmonary hypertension is a subgroup of type 3 pulmonary 
      hypertension (PH) with the recommended treatment limited to oxygen therapy and 
      lacks potential therapeutic targets. To investigate the role of NLRC3 in 
      hypoxia-induced PH and its potential mechanism, we first collected lung tissues 
      of high-altitude pulmonary hypertension (HAPH) patients. Immunohistochemistry and 
      immunofluorescence showed that NLRC3 was downregulated and was mainly 
      co-localized with the smooth muscle cells of the pulmonary vessels in HAPH 
      patients. Besides, we found that NLRC3 was also expressed in endothelial cells in 
      HAPH patients for the first time. Then, wild type (WT) and NLRC3 knockout 
      (NLRC3(-/-)) mice were used to construct hypoxia models and primary pulmonary 
      arterial smooth muscle cells (PASMCs) of rats and endothelial cells were cultured 
      for verification. Right heart catheterization and echocardiography suggested that 
      NLRC3 knockout promoted right ventricular systolic pressure (RVSP) up-regulation, 
      right ventricular hypertrophy and fibrosis in hypoxia-induced mice. This study 
      first demonstrated that NLRC3 deficiency promoted hypoxia-stimulated PASMCs 
      proliferation, Human umbilical vein endothelial cells (HUVECs) apoptosis, 
      migration and inflammation through IKK/NF-kappaB p65/HIF-1alpha pathway in vitro and in 
      vivo, further promoted vascular remodeling and PH progression, which provided a 
      new target for the treatment of hypoxia-induced PH.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Maimaitiaili, Nuerbiyemu
AU  - Maimaitiaili N
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Zeng, Yanxi
AU  - Zeng Y
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Ju, Peinan
AU  - Ju P
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Zhakeer, Gulinigeer
AU  - Zhakeer G
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - E, Guangxi
AU  - E G
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Yao, Hongyun
AU  - Yao H
AD  - Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University, 
      School of Medicine, Shanghai, China.
FAU - Shi, Yefei
AU  - Shi Y
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Zhai, Ming
AU  - Zhai M
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Zhuang, Jianhui
AU  - Zhuang J
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China.
FAU - Peng, Wenhui
AU  - Peng W
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China; Department of Cardiology, Shigatse People's 
      Hospital, Tibet, China. Electronic address: pwenhui@tongji.edu.cn.
FAU - Zhuoga, Deji
AU  - Zhuoga D
AD  - Department of Cardiology, Shigatse People's Hospital, Tibet, China. Electronic 
      address: 488798460@qq.com.
FAU - Yu, Qing
AU  - Yu Q
AD  - Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, 
      School of Medicine, Shanghai, China. Electronic address: daisyyuqing@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230814
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NLRC3 protein, human)
RN  - 0 (NLRC3 protein, mouse)
RN  - 0 (RELA protein, human)
RN  - 0 (HIF1A protein, human)
RN  - Pulmonary edema of mountaineers
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - Rats
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Endothelial Cells/metabolism
MH  - *Hypertension, Pulmonary/genetics/metabolism
MH  - Hypoxia/metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NF-kappa B/metabolism
MH  - Pulmonary Artery/metabolism
MH  - Vascular Remodeling/genetics
OTO - NOTNLM
OT  - Endothelial cells
OT  - Hypoxic pulmonary hypertension
OT  - NLRC3
OT  - Pulmonary arterial smooth muscle cells
COIS- Declaration of competing interest The study complies with ethical consideration. 
      The manuscript has not been published or submitted for publication elsewhere and 
      is not being considered for publication in any other journal.
EDAT- 2023/08/17 00:42
MHDA- 2023/09/18 12:42
CRDT- 2023/08/16 19:21
PHST- 2023/03/08 00:00 [received]
PHST- 2023/08/11 00:00 [revised]
PHST- 2023/08/13 00:00 [accepted]
PHST- 2023/09/18 12:42 [medline]
PHST- 2023/08/17 00:42 [pubmed]
PHST- 2023/08/16 19:21 [entrez]
AID - S0014-4827(23)00303-8 [pii]
AID - 10.1016/j.yexcr.2023.113755 [doi]
PST - ppublish
SO  - Exp Cell Res. 2023 Oct 15;431(2):113755. doi: 10.1016/j.yexcr.2023.113755. Epub 
      2023 Aug 14.