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Recovery of Ischemic Infarction by Trientine‐induced Copper Redistribution in the Heart of Rhesus Monkeys
Author(s) -
Han Pengfei,
Ding Xueqin,
Fu Chunyan,
Zhang Xianyu,
Zhang Wenjing,
Xiao Ying,
Wang Hongge,
Sun Xiaorong,
Fan Suzhen,
Kang Y. James
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1278.3
Subject(s) - medicine , myocardial infarction , cardiology , ligation , ischemic cardiomyopathy , infarction , ischemia , ejection fraction , artery , angiogenesis , heart failure
Persistent myocardial ischemic insult leads to copper (Cu) efflux from the heart and Cu elevation in the plasma, in association with significantly decreased capillary density. Cu is essential for angiogenesis. We observed that Cu‐trientine complex increased Cu uptake by primary cultures of neonatal rat cardiomyocytes subjected to hypoxia. The present study was undertaken to test the hypothesis that Cu redistribution to the heart by trientine can improve recovery of myocardial ischemic infarction. Male Rhesus monkeys of 2–3 years old were subjected to coronary artery ligation to induce myocardial ischemia. One year after the operation, myocardial infarction and dysfunction were detected by MRI and echocardiography. Trientine at a dose of 18 mg/kg a day was administered orally for eight weeks. At the end of the dose regiment, Cu concentrations were significantly elevated in the infarct area and border zone of the ischemic hearts, along with a decrease in plasma Cu concentrations compared to the untreated group. The angiogenesis factors including vascular endothelial growth factor (VEGF), VEGF receptor‐1 (VEGFR‐1), and other relevant factors were activated by the trientine treatment. Along with these changes, myocardial infarct size was significantly decreased and the density of myocardial microvessels was significantly increased. In addition, cardiac function was significantly improved, as evidenced by increased ejection fraction (EF) value. This study thus demonstrates that trientine is capable of redistributing Cu to the heart under ischemic conditions leading to a recovery of myocardial injury and dysfunction in Rhesus monkeys. Support or Funding Information This study is upported by National Science Foundation of China (81230004 and 81300109).