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: Sharad Rastogi, Mayra Guerrero, Mengjun Wang, Itamar Ilsar, Michael S Sabbah, Ramesh C Gupta, Hani N Sabbah
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 300 Issue 4 Pg. H1501-9 (Apr 2011) ISSN: 1522-1539 [Electronic] United States
• PMID: 21217070 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• Hepatocyte Growth Factor

Topics

• Animals
• Calcium-Binding Proteins (biosynthesis)
• Cardiac Output (physiology)
• Disease Progression
• Dogs
• Genetic Therapy (methods)
• Heart Failure (genetics, therapy)
• Hepatocyte Growth Factor (genetics)
• Myocardium
• Plasmids (administration & dosage)
• Sarcoplasmic Reticulum (drug effects, metabolism, physiology)
• Transfection (methods)
• Ventricular Dysfunction, Left (genetics, therapy)
• Ventricular Remodeling (genetics)