PMID- 24507703
OWN - NLM
STAT- MEDLINE
DCOM- 20140905
LR  - 20211021
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 12
DP  - 2014 Feb 8
TI  - Potential therapeutic targets for hypoxia-induced pulmonary artery hypertension.
PG  - 39
LID - 10.1186/1479-5876-12-39 [doi]
AB  - BACKGROUND: Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary 
      disease is characterized by changes of pulmonary vascular reconstruction. 
      Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of 
      factors responsible for the proliferation of hypoxic pulmonary arterial smooth 
      muscle cells (PASMCs), although the exact mechanisms remain unclear. METHODS: 
      Pulmonary artery hypertension was induced in rats with or without 
      5-hydroxydecanoate (5-HD). The mean pulmonary artery pressure, morphologic 
      changes, mRNA and protein expressions of voltage-gated potassium channels (Kv1.5 
      channel), were measured. The concentrations of monocyte chemo-attractant 
      protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-beta1) were detected. 
      Furthermore, pulmonary arterial smooth muscle cells (PASMCs) were isolated and 
      cultured with or without hypoxia pretreated with or without 5-HD or/and Kv1.5 
      inhibitor 4-aminopyridine (4-AP). Mitochondrial membrane potential (Deltapsim) and the 
      proliferation of PASMCs were detected. RESULTS: 5-HD significantly prevented the 
      development of PAH by blocking the mitochondrial membrane depolarization, 
      increased the expression of voltage-gated potassium channels, and reduced 
      pulmonary hypertension mediated by TGF-beta1 or MCP-1 signaling pathway. CONCLUSION: 
      The MitoKATP plays an important role in the development of PAH and may be 
      therapeutic target for the treatment of disease.
FAU - Dong, Li
AU  - Dong L
FAU - Li, Yuping
AU  - Li Y
FAU - Hu, HongLing
AU  - Hu H
FAU - Shi, Lin
AU  - Shi L
FAU - Chen, Junjie
AU  - Chen J
FAU - Wang, Beibei
AU  - Wang B
FAU - Chen, Chaolei
AU  - Chen C
FAU - Zhu, Haiping
AU  - Zhu H
FAU - Li, Yunlei
AU  - Li Y
FAU - Li, Qiu
AU  - Li Q
FAU - Zhang, Liping
AU  - Zhang L
FAU - Chen, Chengshui
AU  - Chen C
AD  - Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou 
      Medical College, Wenzhou 325000, China. chenchengshui@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140208
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
RN  - 0 (Chemokine CCL2)
RN  - 0 (Decanoic Acids)
RN  - 0 (Hydroxy Acids)
RN  - 0 (Kv1.5 Potassium Channel)
RN  - 0 (Potassium Channels)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (mitochondrial K(ATP) channel)
RN  - 624-00-0 (5-hydroxydecanoic acid)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Cell Proliferation/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Decanoic Acids/pharmacology/therapeutic use
MH  - Hydroxy Acids/pharmacology/therapeutic use
MH  - Hypertension, Pulmonary/*drug therapy/*etiology/physiopathology
MH  - Hypoxia/*complications/physiopathology
MH  - Kv1.5 Potassium Channel/genetics/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Models, Biological
MH  - *Molecular Targeted Therapy
MH  - Myocytes, Smooth Muscle/drug effects/metabolism/pathology
MH  - Potassium Channels/metabolism
MH  - Pulmonary Artery/drug effects/metabolism/*pathology/physiopathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC3946029
EDAT- 2014/02/11 06:00
MHDA- 2014/09/06 06:00
PMCR- 2014/02/08
CRDT- 2014/02/11 06:00
PHST- 2013/12/22 00:00 [received]
PHST- 2014/02/05 00:00 [accepted]
PHST- 2014/02/11 06:00 [entrez]
PHST- 2014/02/11 06:00 [pubmed]
PHST- 2014/09/06 06:00 [medline]
PHST- 2014/02/08 00:00 [pmc-release]
AID - 1479-5876-12-39 [pii]
AID - 10.1186/1479-5876-12-39 [doi]
PST - epublish
SO  - J Transl Med. 2014 Feb 8;12:39. doi: 10.1186/1479-5876-12-39.