Okuhara Koichiro, Kisaka Tomohiko, Ozono Ryoji, Kurisu Satoshi, Inoue Ichiro, Soga Junko, Yano Yoko, Oshima Tetsuya, Kihara Yasuki, Yoshizumi Masao
Departments of Cardiovascular Physiology and Medicine, Cardiovascular Medicine, Clinical Laboratory Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
South Med J. 2010 Sep;103(9):876-81. doi: 10.1097/SMJ.0b013e3181eac06a.
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.
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).
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.
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.
血红素加氧酶1（HO-1）可被应激迅速诱导，将促氧化血红素降解为一氧化碳、胆红素和游离铁（Fe）。HO-1的诱导是抵御组织损伤的重要防御机制。在此，我们检验了HO-1在人类急性心肌梗死（AMI）后心肌中被激活的假说。
通过测量血清胆红素和铁水平分析AMI后HO-1活性的变化。在介入治疗后连续收集AMI患者（n = 41）的血样，并与非AMI受试者（n = 18）进行比较。测量了部分AMI患者（n = 12）的HO-1蛋白水平。
在AMI患者中，而非非AMI受试者中，血清胆红素水平（1.57倍，P < 0.001）和铁水平（1.35倍，P < 0.01）短暂升高，两者均在采样开始后18 - 21小时达到峰值。AMI患者胆红素和铁水平的峰值变化彼此显著相关。此外，血清HO-1蛋白水平升高，其变化与胆红素水平变化显著相关（r = 0.82，P < 0.005）。胆红素反应高（峰值水平>0.5 mg/dL）的患者缺血心肌的侧支血流更丰富。
这些结果表明血红素加氧酶（HO）在AMI后被激活，且在血清中可检测到。我们的数据提供了人类应激后HO-1诱导的首个证据。胆红素水平变化可能是AMI后高侧支血流形成的新指标。
