Enhanced expression of hepatocyte growth factor/c-Met by myocardial ischemia and reperfusion in a rat model.
BACKGROUND
Hepatocyte growth factor (HGF) is a multifunctional factor implicated in tissue regeneration, wound healing, and angiogenesis. Circulating HGF is reportedly elevated during the early stage of myocardial infarction. However, its precise effect on the heart is unknown. To evaluate the regulation of HGF in ischemically damaged myocardium, the production of HGF and its high-affinity receptor, c-Met, was studied in a rat model of myocardial ischemia and reperfusion.


RESULTS
The plasma concentration of HGF began to increase within 1 hour of reperfusion after 1 hour of ischemia. The peak level was reached at 3 hours after reperfusion. Northern blotting revealed that HGF mRNA expression in the heart was augmented threefold at 24 and 48 hours and remained elevated by twofold at 120 hours after the myocardium was reperfused. The signal for c-met, high-affinity HGF receptor mRNA, was also upregulated parallel to upregulation for HGF. In the kidney, liver, lung, and spleen, HGF mRNA was also maximally increased at 12 hours after reperfusion. However, c-met was not upregulated in these organs. Immunohistochemical studies disclosed that capillary endothelial and interstitial cells, including infiltrating macrophages, were intensely stained for HGF, whereas capillary endothelial cells in the reperfused myocardium were positive for c-Met.


CONCLUSIONS
This study is the first to show that myocardial ischemia and reperfusion induced HGF expression in various organs in vivo. These results indicate that HGF/c-Met plays a role in capillary endothelial cell regeneration in the ischemically injured heart.
Ono
K
K
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Matsumori
A
A
Shioi
T
T
Furukawa
Y
Y
Sasayama
S
S
D000818:Animals; D017228:Hepatocyte Growth Factor / Q000032:analysis* / Q000096:biosynthesis / Q000097:blood; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000378:metabolism*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000096:biosynthesis
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases