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Open Access Highly Accessed Original investigation

Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2

Xiao Miao13, Yonggang Wang23, Jian Sun2, Weixia Sun23, Yi Tan34, Lu Cai345, Yang Zheng2, Guanfang Su1*, Quan Liu2* and Yuehui Wang1

Author Affiliations

1 Department of Ophthalmology, the Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China

2 The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, China

3 Kosair Children Hospital Research Institute at the Department of Pediatrics, University of Louisville, Louisville, 40202, USA

4 Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical College, Wenzhou, 325035, China

5 Departments of Radiation Oncology and Pharmacology and Toxicology, University of Louisville, Louisville, 40202, USA

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Cardiovascular Diabetology 2013, 12:54  doi:10.1186/1475-2840-12-54

Published: 28 March 2013

Abstract

Background

Cardiovascular diseases remain a leading cause of the mortality world-wide, which is related to several risks, including the life style change and the increased diabetes prevalence. The present study was to explore the preventive effect of zinc on the pathogenic changes in the aorta.

Methods

A genetic type 1 diabetic OVE26 mouse model was used with/without zinc supplementation for 3 months. To determine gender difference either for pathogenic changes in the aorta of diabetic mice or for zinc protective effects on diabetes-induced pathogenic changes, both males and females were investigated in parallel by histopathological and immunohistochemical examinations, in combination of real-time PCR assay.

Results

Diabetes induced significant increases in aortic oxidative damage, inflammation, and remodeling (increased fibrosis and wall thickness) without significant difference between genders. Zinc treatment of these diabetic mice for three months completely prevented the above pathogenic changes in the aorta, and also significantly up-regulated the expression and function of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a pivotal regulator of anti-oxidative mechanism, and the expression of metallothionein (MT), a potent antioxidant. There was gender difference for the protective effect of zinc against diabetes-induced pathogenic changes and the up-regulated levels of Nrf2 and MT in the aorta.

Conclusions

These results suggest that zinc supplementation provides a significant protection against diabetes-induced pathogenic changes in the aorta without gender difference in the type 1 diabetic mouse model. The aortic protection by zinc against diabetes-induced pathogenic changes is associated with the up-regulation of both MT and Nrf2 expression.

Keywords:
Zinc; Vascular damage; Diabetes; Oxidative stress; Nrf2; Metallothionein