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Clin Exp Pharmacol Physiol ; 36(8): 790-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19215239

RESUMO

1. There is growing evidence of the beneficial effects of hepatocyte growth factor (HGF) in myocardial infarction, heart failure and occlusive peripheral arterial disease. The aim of the present study was to evaluate the effects of intracoronary administration of an adenovirus vector encoding the human HGF gene (Ad-HGF) on serum levels of cytokines and mobilization of CD34(+) and CD117(+) cells in patients with coronary heart disease. 2. Twenty-one patients with severe coronary artery disease were recruited to the study: 11 patients received both a stent and administration of Ad-HGF; the remaining 10 patients received a stent alone and served as the control group. Blood samples were obtained from the femoral vein before and then 6 and 24 h, 3 and 6 days and 2 weeks after treatment for the isolation of serum and peripheral blood mononuclear cells. Intracoronary administration of Ad-HGF in patients with coronary heart disease resulted in high levels of HGF gene expression, as well as its receptor c-met, compared with the control group, as demonstrated by real-time reverse transcription-polymerase chain reaction. In addition, serum levels of HGF, vascular endothelial growth factor, monocyte chemoattractant protein-1 and interleukin (IL)-10 were increased and serum levels of IL-8 were decreased in patients administered Ad-HGF compared with the control group. The percentage of CD34(+) and CD117(+) cells in the peripheral blood increased in patients administered Ad-HGF. 3. In conclusion, HGF gene therapy may play an important role in the regulation of cytokines and the induction of endothelial progenitor cell mobilization in patients with coronary heart disease.


Assuntos
Doença das Coronárias/terapia , Citocinas/sangue , Células Endoteliais/metabolismo , Terapia Genética , Fator de Crescimento de Hepatócito/genética , Células-Tronco/metabolismo , Adenoviridae/genética , Idoso , Antígenos CD34/metabolismo , Cateterismo Cardíaco , Quimiocina CCL2/sangue , Circulação Colateral/fisiologia , Doença das Coronárias/genética , Doença das Coronárias/patologia , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Vetores Genéticos , Mobilização de Células-Tronco Hematopoéticas , Fator de Crescimento de Hepatócito/sangue , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Proto-Oncogênicas c-kit/metabolismo , Proteínas Proto-Oncogênicas c-met/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Stents
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