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Prevention of hypoxic pulmonary hypertension by hypoxia-inducible expression of p27 in pulmonary artery smooth muscle cells.
MedLine Citation:
PMID:  24871579     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hypoxia-induced proliferation of pulmonary artery smooth muscle cells (SMCs) is important in the development of hypoxic pulmonary hypertension (HPH). We constructed a lentivirial vector containing a smooth muscle-specific promoter and six copies of hypoxia response element to co-drive the expression of p27, the key cyclin-dependent kinase inhibitor that blocks the G1 to S phase transition in cell cycle progression, in pulmonary artery SMCs in hypoxia. Then in vivo we examined the prevention effects of the vector on HPH in mice and in vitro the specificity on the hypoxia-inducible expression of p27 in pulmonary artery SMCs. Hypobaric hypoxia for 4 weeks resulted in significant increases in the right ventricular systolic pressure, the ratio of right ventricle to left ventricle plus septal weight and the muscularization of pulmonary vessels in mice. Administration of the vector before hypoxia significantly prevented the effects of hypoxia. In vitro, the vector exhibited hypoxic inducibility and relatively specific expression in pulmonary artery SMCs, inhibited the hypoxia-induced proliferation of pulmonary artery SMCs and arrested more cells at G0/G1 phase. These results demonstrate that the hypoxia-inducible p27 expression prevents the development of HPH in mice.Gene Therapy advance online publication, 29 May 2014; doi:10.1038/gt.2014.49.
Authors:
Y Luo; B Zhang; H-Y Dong; Y Liu; Z-C Li; M-Q Dong; Y-Q Gao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-29
Journal Detail:
Title:  Gene therapy     Volume:  -     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-5-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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