Chronic Cadmium Exposure Aggravates the Cardiac Dysfunction in Type 2 Diabetic Mice by Promoting Inflammation and Fibrosis

Abstract Background: Diabetic cardiomyopathy (DCM) is a serious diabetic complication with high mortality. Cadmium (Cd) is a ubiquitous environmental contaminant and plays an important role in cardiac lesions. However, whether Cd aggravates DCM is debatable. In the present study, the effects of chronic Cd exposure on cardiomyopathy in normal and type 2 diabetic mice were investigated. Methods: Sixty male C57BL/6J mice were randomly divided into four groups: blank control (normal mice without Cd exposure), Cd control (normal mice with Cd exposure, exposure level 1.74-2.45 mg/kg/day), diabetic mice control (diabetic mice without Cd exposure) and experimental group (diabetic mice with Cd exposure, exposure level 1.37-3.58 mg/kg/day). After 16 weeks Cd exposure, echocardiography was performed to determine cardiac structure and function. Other outcomes measures included myocardial injury, inflammation and fibrosis. Results: Cd damaged the cardiac function by decreased EF% (ejection fraction) and FS% (fractional shortening) and increased concentration of cTnT (cardiac troponin T) and the expressions of BNP (brain natriuretic peptide) and ANP (atrial natriuretic peptide) in normal mice. For experimental group, the expression of IL-1 (Interleukin-1), TNF-α (tumor necrosis factor-alpha), MCP-1 (monocyte chemotactic protein 1), FN (fibronectin) and TGF-β1 (transforming growth factor-β1) were significantly increased, indicating that Cd promoted the accumulations of fibrosis and inflammation in diabetic mice. In terms of cardiac function, compared with normal mice, the cardiac injury marker of experimental mice was increased and the myocardial contractility was further attenuate, suggesting diabetic mice were more sensitive than normal mice when exposed to cadmium. Conclusion: Cd could damage the heart contractility and aggravate the disruption of cardiac function in diabetic mice by deteriorating inflammation and fibrosis.