Myocardial transfection with naked DNA plasmid encoding hepatocyte growth factor prevents the progression of heart failure in dogs

Sharad Rastogi, Mayra Guerrero, Mengjun Wang, Itamar Ilsar, Michael S. Sabbah, Ramesh C. Gupta, Hani N. Sabbah

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 shamoperated 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.

Original languageEnglish (US)
Pages (from-to)H1501-H1509
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Sarcoplasmic calcium-cycling regulatory proteins
  • Ventricular function and remodeling

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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