title: Long-term effects of hepatocyte growth factor gene therapy in rat myocardial infarct model.
abstract: We investigated the long-term effects of human hepatocyte growth factor (HGF) gene therapy in a rat myocardial infarct model. Treatment adenovirus coexpressing the HGF therapeutic gene and the human sodium/iodide symporter (NIS) reporter gene or control adenovirus expressing the NIS gene alone were injected directly into the infarct border zone immediately after permanent coronary ligation in rats (n=6 each). A uniform disease state was confirmed in the acute phase in terms of impaired left ventricular (LV) function by cine magnetic resonance imaging (MRI), large infarct extent by (99m)Tc-tetrofosmin single-photon emission computed tomography (SPECT) and successful gene transfer and expression by (99m)TcO(4)(-) SPECT. After a 10-week follow-up, repeated cine MRI demonstrated no significant difference in the LV ejection fraction between the time points or groups, but a significantly increased end-diastolic volume from the acute to the chronic phase without a significant difference between the groups. Capillary density was significantly higher in the treatment group, whereas arteriole density remained unchanged. Two-photon excitation fluorescence microscopy revealed extremely thin capillaries (2-5 μm), and their irregular networks increased in the infarct border zone of the treated myocardium. Our results indicated that single HGF gene therapy alone induced an immature and irregular microvasculature.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Jin
authors.forename: M
authors.initials: M
authors.lastname: Inubushi
authors.forename: K
authors.initials: K
authors.lastname: Masamoto
authors.forename: K
authors.initials: K
authors.lastname: Odaka
authors.forename: I
authors.initials: I
authors.lastname: Aoki
authors.forename: A B
authors.initials: AB
authors.lastname: Tsuji
authors.forename: M
authors.initials: M
authors.lastname: Sagara
authors.forename: M
authors.initials: M
authors.lastname: Koizumi
authors.forename: T
authors.initials: T
authors.lastname: Saga
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013995:Time; D016277:Ventricular Function, Left
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor