Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice

Abstract

Zinc (Zn) is an important trace element in the body that has antioxidant effects. It has been proven that Zn deficiency can cause oxidative stress. The purpose of the present study was to clarify the effect and mechanism of Zn deficiency on myocardial fibrosis. Mice were fed with different Zn levels dietary for 9 weeks: Zn-normal group (ZnN, 34 mg Zn/kg), Zn-deficient group (ZnD, 2 mg Zn/kg), and Zn-adequate group (ZnA, 100 mg Zn/kg). We found that the Zn-deficient diet reduced the Zn concentration in myocardial tissue. Moreover, the TUNEL results demonstrated that cardiomyocytes in the ZnD group died in large numbers. Furthermore, ROS levels were significantly increased, and metallothionein (MT) expression levels decreased in the ZnD group. The results of Sirius Red staining indicated an increase in collagen in the ZnD group. Moreover, the ELISA results showed that collagen I, III, and IV and fibronectin (FN) were increased. In addition, the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) was detected by RT-qPCR. The results showed that the expression of TIMP-1 in the ZnD group was increased, while MMPs were decreased. Immunohistochemical results showed an increase in the content of α-smooth muscle actin (α-SMA), while H&E staining showed an increase in interstitial width and a decrease in the number of cardiac cells. All data suggest that Zn deficiency enhances the oxidative stress response of myocardial tissue and eventually triggers myocardial fibrosis.

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Correspondence to Mengyao Guo.

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All animals were obtained from Huazhong Agricultural University Laboratory Animal Research Center (Wuhan, China), according to the animal welfare standards of use, and approved by the Ethical Committee on Animal Research at Huazhong Agricultural University (HZAUMO-2015-12).

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Cao, J., Duan, S., Zhang, H. et al. Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice. Biol Trace Elem Res 196, 145–152 (2020). https://doi.org/10.1007/s12011-019-01902-4

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Keywords

  • Zn deficiency
  • Myocardial fibrosis
  • Oxygen radicals (ROS)
  • Matrix metalloproteinases (MMPs)
  • Extracellular matrix (ECM)