Role of copper and homocysteine in pressure overload heart failure

Area of Science:

• Cardiovascular Biology
• Nutritional Biochemistry
• Molecular Cardiology

Background:

• Elevated homocysteine (hyperhomocysteinemia) is linked to dilated cardiomyopathy.
• Homocysteine impairs copper-dependent enzymes, and copper deficiency is associated with cardiovascular disease.

Purpose of the Study:

• To investigate if copper supplementation can reverse left ventricular hypertrophy (LVH), fibrosis, and endothelial dysfunction in a mouse model of pressure overload-induced dilated cardiomyopathy.

Main Methods:

• Mice underwent transverse aortic constriction (AC) to induce pressure overload, with or without copper supplementation (20 mg/kg diet) for 12 weeks.
• Cardiac function was assessed using echocardiography and electrocardiography.
• Matrix remodeling was evaluated by Western blot analysis of matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinases (TIMPs), and lysyl oxidase (LOX).

Main Results:

• Copper supplementation improved cardiac function in AC mice.
• TIMP-1 levels, elevated in AC mice, normalized with copper treatment.
• MMP-9, TIMP-3, and LOX activity increased with AC but returned to baseline with copper supplementation; TIMP-4 activity was unaffected.

Conclusions:

• Copper supplementation demonstrates a beneficial effect on cardiac function in pressure overload-induced dilated cardiomyopathy.
• These findings suggest copper's potential role in mitigating cardiac remodeling and dysfunction associated with hyperhomocysteinemia.