title: Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs.
abstract: This study examined the effects of localized intramyocardial injections of hepatocyte growth factor (HGF) naked DNA plasmid on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Twenty-one dogs with intracoronary microembolization-induced HF [LV ejection fraction (EF) = 35-40%] were randomized into three treatment groups, namely, high-dose HGF plasmid (4.0 mg, n = 7), low-dose HGF plasmid (0.4 mg, n = 7), and sham-operated controls treated with normal saline (n = 7). A total of 10-15 injections of HGF plasmid or saline were made directly into the anterior wall of LV. LV EF and end-systolic volume (ESV) were measured before randomization (pretreatment) and at the end of 3 mo of follow-up (posttreatment). Treatment effect (Δ) was calculated as the change from pre- to posttreatment. Protein expression of sarcoplasmic reticulum (SR) Ca(2+)-cycling proteins was determined in LV tissue obtained from the sites of HGF injection and remote areas. Low-dose HGF attenuated the decline in EF (ΔEF: -3 ± 1 vs. -8 ± 1%, P < 0.05) and the increase in ESV (ΔESV: 6 ± 2 vs. 10 ± 1 ml, P < 0.05) seen in control sham-operated dogs, whereas high-dose HGF significantly increased EF (ΔEF: 4 ± 1 vs. -8 ± 1%, P < 0.05) and prevented the increase in ΔESV (ESV: -1 ± 1 vs. 10 ± 1 ml, P < 0.05) compared with control dogs. Treatment with high- and low-dose HGF improved the expression of the SR Ca(2+)-cycling proteins compared with controls. In conclusion, regional intramyocardial injections of HGF naked DNA plasmid improve regional and global LV function and prevent progressive LV remodeling.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Heart & Vascular Institute, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: Sharad
authors.initials: S
authors.lastname: Rastogi
authors.forename: Mayra
authors.initials: M
authors.lastname: Guerrero
authors.forename: Mengjun
authors.initials: M
authors.lastname: Wang
authors.forename: Itamar
authors.initials: I
authors.lastname: Ilsar
authors.forename: Michael S
authors.initials: MS
authors.lastname: Sabbah
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D002302:Cardiac Output / Q000502:physiology; D018450:Disease Progression; D004285:Dogs; D015316:Genetic Therapy / Q000379:methods*; D006333:Heart Failure / Q000235:genetics / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D009206:Myocardium; D010957:Plasmids / Q000008:administration & dosage; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014162:Transfection / Q000379:methods*; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000628:therapy; D020257:Ventricular Remodeling / Q000235:genetics
chemical_list: D002135:Calcium-Binding Proteins; D017228:Hepatocyte Growth Factor