title: 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.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing, China. zhijianyangnj@yahoo.com.cn
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Yang
authors.forename: Shun-Lin
authors.initials: SL
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Zhang
authors.forename: You-Long
authors.initials: YL
authors.lastname: Zhang
authors.forename: Wang
authors.initials: W
authors.lastname: Wei
authors.forename: Dong-Chao
authors.initials: DC
authors.lastname: Ma
authors.forename: Lian-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Tie-Bing
authors.initials: TB
authors.lastname: Zhu
authors.forename: Chun-Jian
authors.initials: CJ
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Ke-Jiang
authors.initials: KJ
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.forename: Wen-Zhu
authors.initials: WZ
authors.lastname: Ma
authors.forename: Zu-Ze
authors.initials: ZZ
authors.lastname: Wu
mesh_terms: 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
chemical_list: 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