Table 2.
Clinical and preclinical copper supplementation and copper chelator treatments.
| Study Object | Mutation/Model | Treatment | Treatment Length | Results | Reference |
|---|---|---|---|---|---|
| A patient of 25 months old | Homozygous E140K mutation in SCO2 | Oral copper supplementation (140 μg/day) | 14 months | Improved cardiac hypertrophy and function | [10] |
| A patient’s fibroblasts | Homozygous W66R mutation in COA6 | Copper chloride (25–200 μmol/L) | 7 days | Partially restored protein expression levels of subunits of mitochondrial complex IV | [8] |
| Mice | Ascending aortic constriction | Copper dietary treatment | 6 mg/Cu/kg diet for 4 weeks and 20 mg/Cu/kg diet for another 4 weeks | Restored VEGF expression and angiogenesis | [107] |
| H9C2 cells | Hydrogen peroxide treatment | Copper sulfate (5 μM) | 48 h | Suppressed cardiomyocyte hypertrophy | [108] |
| Mice | Copper-deficient diet from day 3 postdelivery for 4 to 5 weeks | Copper-adequate diet (6 mg/kg) feeding | 4 weeks | Restored cardiac diastolic and systolic function | [122] |
| Hypercholesterolemic patients | Hyperlipidemia | Oral copper supplementation (5 mg/day) |
45 days | Decreased total plasma cholesterol and increased HDL cholesterol | [155] |
| Adult men | Moderate hypercholesterolemia | Oral copper supplementation (2 mg/day) |
4 weeks | Increased both erythrocyte SOD1 and lipoprotein oxidation lag time | [161] |
| Adult women | Moderate hypercholesterolemia | Oral copper supplementation (2 mg/day) |
8 weeks | Elevated erythrocyte SOD1 and plasma CP levels | [162] |
| Yong women | Healthy volunteer | Oral copper supplementation (6 mg/day) |
4 weeks | Increased erythrocyte SOD1 activity and decrease fibrinolytic factor plasminogen activator inhibitor type 1 concentrations | [163] |
| Rats | Type 2 diabetes | Trientine (8–11 mg/day); TETA (20–30 mg/day per rat) |
7–8 weeks | Prevented excessive cardiac collagen deposition, improved cardiac structure and function, and restored antioxidant defense | [165,171,172,173] |
| Diabetic patients | Type 2 diabetes with left ventricular hypertrophy | Trientine (600 mg/day) | 12 months | Decreased left ventricular mass indexed to body surface area (LVMbsa) |
[174,175] |
COA6: cytochrome c oxidase assembly factor 6; CP: ceruloplasmin; HDL: high-density lipoprotein; SCO: synthesis of cytochrome c oxidase; SOD: superoxide dismutase, TETA: triethylenetetramine; VEGF: vascular endothelial growth factor.