Hepatocyte growth factor plays a critical role in the regulation of cytokine production and induction of endothelial progenitor cell mobilization: a pilot gene therapy study in patients with coronary heart disease.
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.
Yang
Zhi-Jian
ZJ
Department of Cardiovascular Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China. zhijianyangnj@yahoo.com.cn
Xu
Shun-Lin
SL
Chen
Bo
B
Zhang
Shu-Lan
SL
Zhang
You-Long
YL
Wei
Wang
W
Ma
Dong-Chao
DC
Wang
Lian-Sheng
LS
Zhu
Tie-Bing
TB
Li
Chun-Jian
CJ
Wang
Hui
H
Cao
Ke-Jiang
KJ
Gao
Wei
W
Huang
Jun
J
Ma
Wen-Zhu
WZ
Wu
Zu-Ze
ZZ
D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D006328:Cardiac Catheterization; D018932:Chemokine CCL2 / Q000097:blood; D003097:Collateral Circulation / Q000502:physiology; D003327:Coronary Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood*; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D019650:Hematopoietic Stem Cell Mobilization; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D015607:Stents
D018952:Antigens, CD34; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met