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Zinc deficiency worsens and zinc supplement prevents the development of diabetic cardiomyopathy, respectively, in the db/db mice: A key role of Nrf2
Author(s) -
Wang Bowei,
Wang Shudong,
Tong Jian,
Wang Yuehui,
Cai Lu
Publication year - 2017
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.31.1_supplement.843.17
Subject(s) - zinc deficiency (plant disorder) , diabetic cardiomyopathy , ctgf , endocrinology , medicine , oxidative stress , cardiomyopathy , zinc , ventricle , pathogenesis , muscle hypertrophy , fibrosis , micronutrient , chemistry , heart failure , pathology , growth factor , receptor , organic chemistry
Diabetic cardiomyopathy (DCM) is highly prevalent in the type 2 diabetic (T2DM) patients. Zinc is one of the important essential trace metals, and its deficiency associates with various chronic pathogenesis, including vascular diseases. We used B6.BKS(D)‐Leprdb/J (db/db) mice as a T2DM mouse models and provided mice, for six months, with normal diet containing three levels of zinc: deficient, adequate, and supplemented, to explore the role of zinc in the development or progression of DCM. Cardiac function, reflected by the EF%, was significantly decreased along with increases in left ventricle mass and the ratio of heart weight to tibial length, in the db/db mice. As molecular cardiac hypertrophy marker, ANP protein was also significantly increased in db/db mice. The cardiac dysfunction and hypertrophy were also accompanied with significant increases in fibrotic responses (accumulated collagens and increased TGF‐β and CTGF expression) and inflammatory responses and signalings (increased expression of TNF‐α, IL‐1β, CARD9, and BCL10 and activated p38 MAPK) in the heart of db/db mice. All these diabetic effects were exacerbated and ameliorated by zinc deficiency and zinc supplement, respectively. Mechanistically the oxidative stress and damage, mirrored by 3‐NT and 4‐HNE, was significantly increased along with significant decrease in the expression of Nrf2 and its down‐stream antioxidants (NQO‐1 and catalase), which was exacerbated and ameliorated by zinc deficiency and zinc supplement, respectively, in the heart of the db/db mice. These results suggest that zinc deficiency worsens the pathological progression of cardiac disorders in type 2 diabetic db/db mice, which can be significantly prevented by zinc supplement, all which may be related to the role of Nrf2 in the prevention of DCM development and progression. Support or Funding Information This work was supported in part by the Scholarship of China Scholarship Council(No.201506175180)