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Role of Copper and Homocysteine in Pressure Overload Heart Failure
Author(s) -
Hughes William Michael,
Rodriguez Walter E,
Rosenberger Dorothea S,
Moshal Karni S.,
Sen Utpal,
Chen Jing,
Kang Y. James,
Tyagi Suresh C.
Publication year - 2008
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.22.1_supplement.1210.16
Subject(s) - pressure overload , medicine , homocysteine , hyperhomocysteinemia , ventricle , heart failure , copper deficiency , endocrinology , fibrosis , western blot , cardiac function curve , cardiology , dilated cardiomyopathy , lysyl oxidase , matrix metalloproteinase , chemistry , copper , biochemistry , enzyme , cardiac hypertrophy , organic chemistry , gene
Elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) causes dilated cardiomyopathy (DCM). Hcy chelates copper and impairs copper‐dependent enzymes. To test the hypothesis that copper supplement regresses left ventricle hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM hearts (Figure 1), we created aortic constriction (AC) in mice and treated with or without 20 ppm copper supplements in diet for 16 weeks. The mice were grouped as sham; AC, sham+Cu; and AC+Cu. The cardiac function was assessed by ECG and Echocardiography. The levels of fibrosis was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and lysl oxidase (LOX) by zymography and Western blot analyses. The results suggest that cardiac function was restored with copper supplement. Fractional shortening was 51.3±0.9% in AC; 62.7±3.7% in sham; 60.9±4.7% in sham+Cu; and 62.8±3.1% in AC+Cu. The QRS complexes from ECG were: 13.0±1.4 ms in sham; 14.0±2.8 ms in AC; and 13.0±2.1 ms in AC+Cu. Western blot analyses show that MMP‐13, TIMP‐3, and TIMP‐4 activity decreases in AC and then is improved in AC+Cu. TIMP‐1 and LOX activity increases in AC and returns to sham value in AC+Cu. The data suggests that copper supplement restores cardiac function in a pressure overload DCM heart.