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Regression of pressure overload‐induced cardiac hypertrophy by TETA‐mediated myocardial copper supplementation in rats
Author(s) -
Liu Jiaming,
Liu Yinjie,
Sun Xiaorong,
Fan Suzhen,
Ding Xueqin,
Qiu Liying,
Han Pengfei,
Kang Y. James
Publication year - 2018
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.2018.32.1_supplement.580.7
Subject(s) - medicine , pressure overload , muscle hypertrophy , endocrinology , copper , ventricle , ventricular hypertrophy , copper deficiency , cardiac hypertrophy , blood pressure , left ventricular hypertrophy , chemistry , organic chemistry
Sustained pressure overload leads to cardiac hypertrophy and copper efflux from the heart. Dietary copper supplementation replenishes copper in the heart and reverses cardiac hypertrophy. On the contrary, a copper selective chelator, trientine (TETA), reverses left ventricular hypertrophy associated with diabetes. The present study was undertaken to test the hypothesis that TETA functions as a copper chaperone delivering copper to the heart leading to regression of cardiac hypertrophy. Adult male Sprague‐Dawley rats were subjected to transverse aortic constriction (TAC) to induce cardiac hypertrophy. Eight weeks after the surgery cardiac hypertrophy was developed and myocardial copper was reduced. TETA was then administrated by gavage at two different doses (21.9 mg/kg·day and 87.6 mg/kg·day) for six weeks. The results showed that at lower dose, TETA replenished copper contents in the heart, accompanied by a decrease in blood plasma and an increase in urine of copper concentrations. At higher dose, TETA did not replenish copper contents in the heart, but markedly increased copper concentrations in the urine, along with a decrease in serum copper concentrations. Corresponding to myocardial copper repletion, lower dose TETA reversed cardiac hypertrophy, as judged by a reduction in the left ventricle wall thickness (LVAW d and LVPW d ) and a decrease in the heart size (heart weight/tibia length), and diminished cardiac fibrosis, as reflected by a decrease in collagen I content. TETA at higher dose not only did not regressed cardiac hypertrophy, but caused cardiac hypertrophy in sham‐operated rats. This study demonstrates that TETA, at lower dose, functioned as a copper chaperone delivering copper to the heart of copper deprivation and, at higher dose, simply remained its chelator function removing copper from the body by urinary excretion. Support or Funding Information Supported by National Science Foundation of China (81230004 and 81300109). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .