A potential cardioprotective role of hepatocyte growth factor in myocardial infarction in rats.

Abstract

OBJECTIVE:

Cardiotrophic growth factors with anti-cell death actions on cardiac myocytes have gained attention for treatment of patients with myocardial infarction. Hepatocyte growth factor (HGF) plays a role in tissue repair and protection from injuries, however, the physiological role of HGF in the myocardium has not been well defined. We asked if HGF would afford to the infarcted myocardium.

METHODS AND RESULTS:

Mature cardiac myocytes prepared from adult rats expressed barely detectable levels of the c-Met/HGF receptor, however, c-Met receptor expression increased during cultivation, which meant that cardiac myocytes are potential targets of HGF. Addition of hydrogen peroxide remarkably decreased the number of viable mature cardiac myocytes in primary culture, whereas treatment with HGF enhanced survival of the cells subjected to the oxidant stress. Although very low levels of c-Met/HGF receptor and HGF mRNA expression were seen in normal rat hearts, both c-Met/HGF receptor and HGF mRNA levels rapidly increased to much higher levels than normal, when the rats were subjected to myocardial infarction. Immunohistochemical analysis of the c-Met receptor indicated that this receptor was expressed in cardiomyocytes localized in the border regions of the viable myocardium and in non-infarcted regions following myocardial infarction.

CONCLUSION:

The c-Met/HGF receptor is induced in cardiomyocytes following myocardial infarction and HGF exhibits protective effect on cardiomyocytes against oxidative stress. Our working hypothesis is that HGF may afford myocardial protection from myocardial infarction.

• Authors: H Ueda, T Nakamura, K Matsumoto, Y Sawa, H Matsuda, T Nakamura
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 51 Issue 1 Pg. 41-50 (Jul 2001) ISSN: 0008-6363 [Print] England
• PMID: 11399246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins
• RNA, Messenger
• Hepatocyte Growth Factor
• Insulin-Like Growth Factor I
• Hydrogen Peroxide
• Proto-Oncogene Proteins c-met
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Blotting, Western (methods)
• Cell Death (drug effects)
• Cells, Cultured
• Enzyme Activation (drug effects)
• Hepatocyte Growth Factor (genetics, metabolism, pharmacology)
• Humans
• Hydrogen Peroxide (pharmacology)
• Immunohistochemistry
• Insulin-Like Growth Factor I (pharmacology)
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinases (metabolism)
• Myocardial Infarction (metabolism)
• Myocardium (chemistry, metabolism)
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt
• Proto-Oncogene Proteins c-met (analysis, genetics, metabolism)
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)