title: Effects of recombinant adenovirus hepatocyte growth factor gene on myocardial remodeling in spontaneously hypertensive rats.
abstract: OBJECTIVE
  Myocardial hypertrophy and fibrosis are important determinants of congestive heart failure. Previous work has shown that hepatocyte growth factor (HGF) can reduce acute myocardial injury and tissue fibrosis. This study was designed to examine the effects of HGF on myocardial remodeling following sustained hypertension.
  
  
  RESULTS
  There were 4 experimental groups (n = 6) that included spontaneously hypertensive rats (SHRs) injected with 0.1 mL of adenovirus (Ad)-null into the left ventricular (LV) free wall, SHR injected with 0.1 mL of Ad-HGF gene (5 × 10(9) pfu/mL), and SHR injected with 0.1 mL of normal saline, and Wistar Kyoto rats injected with 0.1 mL of Ad-null served as control. At 4 weeks after injection, rats were sacrificed, and HGF expression, myocardial fibrosis, and LV function were determined. We observed that HGF protein expression was reduced in the hearts of SHR (P < .05 vs normal control) and it was markedly increased in SHR injected with Ad-HGF (P < .01 vs SHR injected with Ad-null). Myocardial fibrosis, collagen I, LV mass index (LVMI), and LV end-diastolic pressure (LVEDP) were increased and -dP/dtmax was decreased in SHR injected with Ad-null or normal saline (P < .01 vs normal control). Upregulation of myocardial HGF expression in SHR significantly suppressed myocardial fibrosis, collagen I content, LVMI, LVEDP, and increased -dP/dtmax (all P < .05 vs SHR-Ad-null, n = 6).
  
  
  CONCLUSIONS
  These findings indicate that HGF expression is attenuated in hypertrophic and fibrotic myocardium of SHR. The forced increase in HGF exerts a salutary effect on myocardial fibrosis, collagen I expression, and hemodynamic parameters.
authors.affiliation: Division of Cardiology, the First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Ze-Ping
authors.initials: ZP
authors.lastname: Hu
authors.forename: Yong
authors.initials: Y
authors.lastname: Bao
authors.forename: Da-Nian
authors.initials: DN
authors.lastname: Chen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Dayuan
authors.initials: D
authors.lastname: Li
authors.forename: Bang-Ning
authors.initials: BN
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005355:Fibrosis; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006973:Hypertension / Q000503:physiopathology / Q000628:therapy*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015854:Up-Regulation
chemical_list: D017228:Hepatocyte Growth Factor
keywords: HGF; gene expression; gene therapy; hemodynamic.; myocardial remodeling