Myocardial protective effect of human recombinant hepatocyte growth factor for prolonged heart graft preservation in rats

Masahiro Ryugo, Yoshiki Sawa, Masamichi Ono, Norihide Fukushima, Alexey N. Aleshin, Shinya Mizuno, Toshikazu Nakamura, Hikaru Matsuda

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background. In heart transplantation, myocardial apoptosis during hypothermic storage contributes to graft dysfunction. On the other hand, hepatocyte growth factor (HGF) has been reported to be an antiapoptotic factor in the heart. Therefore, we assessed whether the administration of recombinant human HGF (rh-HGF) prevents apoptosis in the prolonged preserved myocardium, resulting in an improvement in the cardiac function of the graft. Methods. Isolated rat hearts were subjected to 4 hr (group A), 6 hr (group B), and 8 hr (group C: without rh-HGF vs. group D: with 100 μg of rh-HGF) of hypothermic storage followed by 60 min of normothermic reperfusion (n=5 in each group). Results. Compared with non-HGF-treated hearts (group C), HGF-treated hearts (group D) showed a significantly higher recovery rate of left ventricular developed pressure (38±5% vs. 58±6%, P≤0.01) and maximum dp/dt (53±7% vs. 74±4%, P≤0.01) and a lower rate of TUNEL-positive cardiomyocytes (7.8±6.0% vs. 25.3±8.9%, P<0.05) after 60 min of reperfusion. Western blot analysis revealed that c-Met/HGF receptor expression was stronger in the HGF-treated myocardium than in the non-HGF-treated myocardium after 8 hr of storage and was associated with a weaker expression of caspase-3 and a stronger expression of Bcl-xL after 60 min of reperfusion. Conclusion. The administration of rh-HGF before storage improved cardiac function after prolonged myocardial preservation by preventing apoptosis through the c-Met/HGF receptor. Thus, the addition of rh-HGF in the storage solution may be a promising strategy for prolonged heart graft preservation.

Original languageEnglish
Pages (from-to)1153-1158
Number of pages6
JournalTransplantation
Volume78
Issue number8
DOIs
StatePublished - 27 Oct 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Heart preservation
  • Recombinant human HGF
  • c-Met/HGF receptor

Fingerprint

Dive into the research topics of 'Myocardial protective effect of human recombinant hepatocyte growth factor for prolonged heart graft preservation in rats'. Together they form a unique fingerprint.

Cite this