Restoration of myocellular copper-trafficking proteins and mitochondrial copper enzymes repairs cardiac function in rats with diabetes-evoked heart failure.

Diabetes impairs systemic copper regulation, and acts as a major independent risk factor for heart failure (HF) wherein mitochondrial dysfunction is a key pathogenic process. Here we asked whether diabetes might alter mitochondrial structure/function and thus impair cardiac performance by damaging myocellular pathways that mediate cell-copper homeostasis. We measured activity of major mitochondria-resident copper-enzymes cytochrome c oxidase (mt-Cco) and superoxide dismutase 1 (mt-Sod1); expression of three main mitochondrial copper-chaperones [Cco copper chaperone 17 (Cox17), Cox11, and mitochondria-resident copper chaperone for Sod1 (mt-Ccs)]; of copper-dependent Cco-assembly protein Sco1; and regulation of mitochondrial biogenesis, in left-ventricular (LV) tissue from groups of non-diabetic-control, untreated-diabetic, and divalent-copper-selective chelator-treated diabetic rats.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation.

Background: Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM.

Methods: Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment.