Change in bilirubin level following acute myocardial infarction is an index for heme oxygenase activation.
OBJECTIVE
Heme oxygenase 1 (HO-1) is rapidly induced by stress, degrading pro-oxidant heme into carbon monoxide, bilirubin, and free iron (Fe). Induction of HO-1 is an important defense mechanism against tissue injury. Here, we tested the hypothesis that HO-1 is activated in the myocardium after acute myocardial infarction (AMI) in humans.


METHODS
Changes in the HO-1 activity after AMI were analyzed by measuring serum levels of bilirubin and Fe. Blood samples were collected in patients with AMI (n = 41) serially after the interventional therapy and compared with non-AMI subjects (n = 18). HO-1 protein levels were measured in a sample of AMI patients (n = 12).


RESULTS
In AMI patients, but not in non-AMI subjects, serum levels of bilirubin (1.57 fold, P < 0.001) and Fe (1.35 fold, P < 0.01) were transiently elevated, both levels peaking 18-21 hours after the start of sampling. The peak changes in the levels of bilirubin and Fe in AMI patients were significantly correlated with each other. Furthermore, the serum HO-1 protein level was elevated, and its change was significantly correlated with the change in bilirubin level (r = 0.82, P < 0.005). Those with a high bilirubin response (peak levels >0.5 mg/dL) had richer collateral flow into the ischemic myocardium.


CONCLUSIONS
These results suggest that heme oxygenase (HO) was activated following AMI, and it was detectable in the serum. Our data provide the first evidence of HO-1 induction following stress in humans. The change in bilirubin level may be a novel index for high collateral flow formation following AMI.
Okuhara
Koichiro
K
Departments of Cardiovascular Physiology and Medicine, Cardiovascular Medicine, Clinical Laboratory Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Kisaka
Tomohiko
T
Ozono
Ryoji
R
Kurisu
Satoshi
S
Inoue
Ichiro
I
Soga
Junko
J
Yano
Yoko
Y
Oshima
Tetsuya
T
Kihara
Yasuki
Y
Yoshizumi
Masao
M
D000368:Aged; D001663:Bilirubin / Q000097:blood*; D016022:Case-Control Studies; D003097:Collateral Circulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051547:Heme Oxygenase-1 / Q000097:blood*; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000097:blood*; D009206:Myocardium / Q000378:metabolism
D007501:Iron; D051547:Heme Oxygenase-1; D001663:Bilirubin