Elevated COMMD1 Contributes to Cardiomyocyte Copper Efflux in Chronic Myocardial Ischemia: Insights From Rhesus Monkey

作者：Chen Li, Da Li, Xia Cheng, Xiaoli Yuan, Ning Du, Xin Liao, Xiaorong Feng, Jie Yao, Chenglong Li, Chengxia Xie, Mu Yang · 发表于：Cell Proliferation · 年份：2025 · DOI：10.1111/cpr.70016 · 被引用次数：5 · 研究领域：Trace Elements in Health、Cardiac Ischemia and Reperfusion、Cardiac electrophysiology and arrhythmias

Copper deficiency, commonly observed in myocardial infarction, leads to cardiomyocyte loss and cardiac dysfunction, yet the mechanism driving copper efflux remains unclear. To further elucidate the relationship between copper transporters and cardiac copper efflux during chronic myocardial ischemia, a rhesus monkey model was established by performing the permanent ligation of the left anterior descending coronary artery. A dramatic decrease in copper concentration within ischemic cardiomyocytes was observed alongside declining cardiac function. Among major copper transporters, COMMD1 and ATP7B were significantly upregulated in the ischemic myocardium. COMMD1 was specifically localised in cardiomyocytes undergoing copper efflux, whereas increased ATP7B was restricted to cardiac fibroblasts. This indicates that elevated COMMD1 regulates copper efflux in cardiomyocytes during chronic myocardial ischemia, functioning independently of its interactions with P-type ATPase transporters. Given the discrepancy between RNA and protein levels of COMMD1 in ischemic myocardium, post-translational modification is likely responsible for regulating COMMD1 expression. We found that the copper-binding protein with E3 ubiquitin ligase activity, XIAP, augmented before the rise in COMMD1 expression within ischemic cardiomyocytes. Excessive XIAP specifically interacted with COMMD1 to enhance its protein levels under copper-deprivation conditions and vice versa. Overall, our findings reveal a positi...