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Gene Ther ; 21(11): 931-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25077774

RESUMO

Pulmonary hypertension is a life-threatening medical condition, and a growing body of evidence shows that the expression of connective tissue growth factor (CTGF) is significantly associated with its pathogenesis, making it an attractive therapeutic target. Our earlier work revealed that plasmid-based CTGF-specific short hairpin RNA (shRNA) could attenuate pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in rats exposed to cigarette smoke. In this study, we explored the therapeutic role of this shRNA plasmid in the treatment of monocrotaline-induced pulmonary vascular remodeling in rats, and demonstrated that the upregulation of CTGF in PASMCs following a single injection of monocrotaline could be attenuated by administration of the shRNA. Accordingly, this shRNA was found to repress monocrotaline-induced pulmonary vascular remodeling, as evidenced by its ability to reduce the percentage of muscularized vessels and the wall thickness of pulmonary vessels. We concluded that plasmid-based shRNA against CTGF attenuated pulmonary vascular remodeling in monocrotaline-treated rats. CTGF might be a potential target for the treatment of pulmonary vascular remodeling and pulmonary hypertension.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Hipertensão Pulmonar/terapia , RNA Interferente Pequeno/administração & dosagem , Remodelação Vascular , Animais , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Masculino , Monocrotalina , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos
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