Background

Ceruloplasmin (Cp) is a major copper-binding protein produced in the liver and delivers copper to extrahepatic organs. Patients with myocardial infarction are often featured by an elevation of serum copper concentrations due to copper efflux from ischemic hearts. The present study was undertaken to test the hypothesis that serum copper elevation leads to up-regulation of hepatic Cp in myocardial infarction.

Methods

Adult male Sprague-Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper-transporting P-type ATPase (Atp7b), were determined from blood and liver samples collected on day 1, 4, or 7 after the operation.

Results

Serum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, Atp7b, were also significantly increased in the liver. Furthermore, inhibiting the increase of serum copper by a copper chelator, triethylenetetramine (TETA), effectively abolished the elevated Cp activity after LAD ligation.

Conclusion

These results indicate that serum Cp elevation in response to myocardial ischemia most likely resulted from the increased hepatic Cp production, which in turn was more responsive to serum copper elevation than inflammatory response following myocardial ischemia.

中文翻译：

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大鼠心肌缺血模型肝铜蓝蛋白产生的逆向调控

背景

铜蓝蛋白 (Cp) 是肝脏中产生的主要铜结合蛋白，可将铜输送至肝外器官。由于铜从缺血心脏流出，心肌梗塞患者通常以血清铜浓度升高为特征。本研究旨在检验血清铜升高导致心肌梗塞中肝 Cp 上调的假设。

方法

成年雄性 Sprague-Dawley 大鼠接受左前降支 (LAD) 冠状动脉结扎以诱发心肌梗塞。血清铜和 Cp 水平，以及肝 Cp 和铜转运 P 型 ATP 酶 (Atp7b) 的变化是从手术后第 1、4 或 7 天收集的血液和肝脏样本中确定的。

结果

LAD 结扎后第 4 天血清铜浓度显着增加，同时血清 Cp 水平和活性增加。同时，肝脏中 Cp 和铜输出蛋白 Atp7b 的蛋白质水平也显着增加。此外，通过铜螯合剂三亚乙基四胺 (TETA) 抑制血清铜的增加，有效地消除了 LAD 结扎后升高的 Cp 活性。

结论

这些结果表明，响应于心肌缺血的血清 Cp 升高最有可能是由于肝脏 Cp 产生的增加，而肝脏 Cp 生成对血清​​铜升高的反应比心肌缺血后的炎症反应更敏感。