PMID- 25895668
OWN - NLM
STAT- MEDLINE
DCOM- 20160208
LR  - 20211227
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 35
IP  - 6
DP  - 2015
TI  - Modulation of Pulmonary Vascular Remodeling in Hypoxia: Role of 
      15-LOX-2/15-HETE-MAPKs Pathway.
PG  - 2079-97
LID - 10.1159/000374015 [doi]
AB  - BACKGROUND: We have previously shown that 15-hydroxyeicosatetraenoic acid 
      (15-HETE) plays a critical role in pulmonary hypertension (PH)-associated 
      vascular remodeling. However, the signaling mechanisms remain unclear. The 
      purpose of this study was to investigate the role of 15-lipoxygenase-2 
      (15-LO-2)/15-HETE-mitogen-activated protein kinases (MAPKs) pathway in 
      hypoxia-induced pulmonary vascular remodeling and the underlying mechanisms. 
      METHODS: The arterial wall thickness was measured by hematoxylin and eosin (HE) 
      staining in distal pulmonary arteries isolated from normal and PAH 
      patient-derived lungs. The protein expression of phosphorylated extracellular 
      signal-regulated kinase (p-ERK) and phosphorylated p38 mitogen-activated protein 
      kinases (p-p38MAPK) were measured by Western blot in the lungs of PAH patients 
      and hypoxia-induced rats. The apoptosis of cultured rat pulmonary arterial smooth 
      muscle cells (PASMCs) was determined by Terminal deoxynucleotidyl transferase 
      dUTP nick end labeling (TUNEL) and Flow cytometry. The cell proliferation and 
      cell cycle in PASMCs following hypoxia were analyzed by bromodeoxyuridine 
      incorporation and flow cytometry, respectively. RESULTS: Our results showed that 
      the levels of p-ERK and p-p38MAPK were both drastically elevated in lungs from 
      human patients and hypoxic rats. The HE staining revealed that the medial wall 
      thickness was higher in patients with PAH than normal humans. In cultured PASMCs, 
      Hypoxia stimulated the cell proliferation, the cell cycle progression, and 
      subsequently promoted cell differentiation and cell migration leading to the 
      suppressed cell apoptosis. Furthermore, MAPKs- induced cell proliferation and 
      anti-apoptosis in PASMCs is 15-LO-2/15HETE activation-dependent. CONCLUSION: Our 
      study indicates that hypoxia-induced pulmonary vascular remodeling is associated 
      with increased levels of 15-LO-2 and 15-HETE. 15-LO-2/15-HETE stimulates the cell 
      proliferation and anti-apoptosis in PASMCs through phosphorylation of ERK and 
      p38MAPK, which subsequently contributing to hypoxia-induced pulmonary vascular 
      remodeling.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Yu, Xiufeng
AU  - Yu X
AD  - Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical 
      University (Daqing), Daqing, China.
FAU - Li, Tingting
AU  - Li T
FAU - Liu, Xia
AU  - Liu X
FAU - Yu, Hao
AU  - Yu H
FAU - Hao, Zhongfei
AU  - Hao Z
FAU - Chen, Yingli
AU  - Chen Y
FAU - Zhang, Chen
AU  - Zhang C
FAU - Liu, Yumei
AU  - Liu Y
FAU - Li, Qian
AU  - Li Q
FAU - Mao, Min
AU  - Mao M
FAU - Zhu, Daling
AU  - Zhu D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150407
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
RN  - EC 1.13.11.33 (ALOX15B protein, human)
RN  - EC 1.13.11.33 (Arachidonate 15-Lipoxygenase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
EIN - Cell Physiol Biochem. 2021;55(6):812-813. PMID: 34958728
MH  - Adult
MH  - Animals
MH  - Apoptosis/physiology
MH  - Arachidonate 15-Lipoxygenase/*metabolism
MH  - Cell Cycle/physiology
MH  - Cell Differentiation/physiology
MH  - Cell Movement/physiology
MH  - Cell Proliferation/physiology
MH  - Cells, Cultured
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/*metabolism
MH  - Hypoxia/metabolism/*physiopathology
MH  - Lung/metabolism/*physiology
MH  - Male
MH  - Muscle, Smooth, Vascular/metabolism/physiology
MH  - Myocytes, Smooth Muscle/metabolism/physiology
MH  - Pulmonary Artery/metabolism/*physiology
MH  - Rats
MH  - Signal Transduction/physiology
MH  - Vascular Remodeling/*physiology
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2015/04/22 06:00
MHDA- 2016/02/09 06:00
CRDT- 2015/04/22 06:00
PHST- 2015/02/13 00:00 [accepted]
PHST- 2015/04/22 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/02/09 06:00 [medline]
AID - 000374015 [pii]
AID - 10.1159/000374015 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;35(6):2079-97. doi: 10.1159/000374015. Epub 2015 Apr 
      7.