title: Hepatocyte growth factor improves the survival of rats with pulmonary arterial hypertension via the amelioration of pulmonary hemodynamics.
abstract: Hepatocyte growth factor (HGF) is a multifunctional growth factor with mitogenic, anti-apoptotic and anti-fibrotic activities. In this study, we investigated the effect of administration of recombinant human HGF on pulmonary arterial hypertension. Pulmonary arterial hypertension was induced in rats by a single injection of monocrotaline (MCT) and recombinant human HGF (0.12 mg/day) was administered into the right ventricle cavity using osmotic pumps, which were implanted subcutaneously 21 days after MCT injection. Continuous intravenous delivery of recombinant human HGF for 14 days led to prolonged survival of animals suffering from severe MCT-induced pulmonary arterial hypertension. Although a bolus injection of recombinant human HGF did not affect pulmonary arterial pressure, a 14-day administration of recombinant human HGF attenuated the inflammatory cell infiltrate, matrix accumulation and vascular medial thickening. As a consequence, the pulmonary lumen was enlarged and the pulmonary arterial pressure was significantly reduced. Additionally, continuous administration of recombinant human HGF suppressed lung tissue expression of platelet-derived growth factor, which plays an important role in the development of pulmonary arterial hypertension. These results indicate that recombinant human HGF possibly has a great potential for improving symptoms and altering the clinical course of pulmonary arterial hypertension.
authors.affiliation: Digestive Disease and Life-Style Related Disease, Kagoshima University Graduate School of Medical and Dental Sciences, 3-35-1 Sakuragaoka, Kagoshima, Japan.
authors.forename: Kiyohisa
authors.initials: K
authors.lastname: Hiramine
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sata
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.forename: Ryozo
authors.initials: R
authors.lastname: Kamimura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Setoyama
authors.forename: Kou
authors.initials: K
authors.lastname: Arai
authors.forename: Norihito
authors.initials: N
authors.lastname: Nuruki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Uto
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis; D003251:Constriction, Pathologic / Q000188:drug therapy; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D015121:6-Ketoprostaglandin F1 alpha; D017228:Hepatocyte Growth Factor; D016686:Monocrotaline; D002097:C-Reactive Protein