Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice
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Zinc Deficiency Promoted Fibrosis via ROS and TIMP/MMPs in the Myocardium of Mice Jing-wen Cao 1 & Shi-yu Duan 1 & Hong-xin Zhang 1 & Yu Chen 1 & Mengyao Guo 1 Received: 11 August 2019 / Accepted: 11 September 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019
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. Keywords Zn deficiency . Myocardial fibrosis . Oxygen radicals (ROS) . Matrix metalloproteinases (MMPs) . Extracellular matrix (ECM)
Introduction Heart disease remains the main global cause of death, accounting for 150 million deaths per year, a number that is expected to grow [1]. However, due to the complex physiological functions of the heart, we know little about the pathological mechanism of heart disease. To date, there are two main arguments, myocardial pathological reconstruction leads to the occurrence and evolution of heart disease, and myocardial cell death leads to the occurrence and development of heart disease. Among them, myocardial pathological reconstruction is currently considered to be the most important factor causing the occurrence of heart disease [2, 3]. In addition, studies have shown that the degree of ECM remodeling determines the
* Mengyao Guo [email protected] 1
Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China
progression of heart disease, especially cardiac failure [4–6]. It should be noted that myocardial cell death and myocardial remodeling are mutually affected The main pathological featu
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