Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin

Jota Nakano*, Akira Marui, Hiroyuki Muranaka, Hidetoshi Masumoto, Hisashi Noma, Yasuhiko Tabata, Akio Ido, Hirohito Tsubouchi, Tadashi Ikeda, Ryuzo Sakata

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objectives: Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model. Methods: Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity. Results: At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group. Conclusions: Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis.

Original languageEnglish (US)
Pages (from-to)300-307
Number of pages8
JournalInteractive cardiovascular and thoracic surgery
Volume18
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • Fibrosis
  • Growth substances
  • Myocarditis

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin'. Together they form a unique fingerprint.

  • Cite this

    Nakano, J., Marui, A., Muranaka, H., Masumoto, H., Noma, H., Tabata, Y., Ido, A., Tsubouchi, H., Ikeda, T., & Sakata, R. (2014). Effects of hepatocyte growth factor in myocarditis rats induced by immunization with porcine cardiac myosin. Interactive cardiovascular and thoracic surgery, 18(3), 300-307. https://doi.org/10.1093/icvts/ivt512