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Copper‐Induced Reversal of Fibrosis in Rat Model of Cardiac Hypertrophy is Associated with Enhanced Collagen Degradation by MMP‐2 Up‐Regulation
Author(s) -
Liu Yinjie,
Xiao Ying,
Liu Jiaming,
Han Pengfei,
Feng Li,
Kang Y. James
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.637.3
Subject(s) - sirius red , fibrosis , pressure overload , muscle hypertrophy , lysyl oxidase , western blot , cardiac fibrosis , hydroxyproline , matrix metalloproteinase , medicine , endocrinology , pathological , cardiac hypertrophy , chemistry , copper deficiency , pathology , copper , biochemistry , extracellular matrix , organic chemistry , gene
Our recent studies observed that trientine (TETA), a copper chelator, is capable of redistributing copper from plasma to the heart, leading to regression of cardiac fibrosis in rat model of pressure overload‐induced heart hypertrophy. The present study was undertaken to explore possible mechanisms by which copper repletion reverses cardiac fibrosis. Adult male Sprague‐Dawley rats were subjected to ascending aortic constriction (AAC) to induce pathological cardiac hypertrophy. Four months after the operation, cardiac hypertrophy along with fibrosis was fully developed as determined by pathological examination and Sirius red staining. At the same time, TETA at a dose of 4.38 mg/kg, twice a day, was administered orally for six weeks. At the end of the experiment, the expression and crosslinking of type I and III collagens were determined respectively by immunohistochemistry and Sircol collagen assay. Western blot was performed to detect the expressions of lysyl oxidase (LOX), MMP‐2 and MMP‐9. The results showed that the content and crosslinking of type I and III collagens were both significantly decreased after TETA treatment. The expression of MMP‐2 was up‐regulated, but the expressions of MMP‐9 and LOX were not changed. The data thus demonstrated that the reversal of cardiac fibrosis by TETA‐induced copper repletion is related at least in part to an enhanced collagen degradation process. Support or Funding Information This study is supported by National Science Foundation of China (81230004 and 81300109).