Cadmium, an Environmental Contaminant with a Potential Role In Modulating Cardiac Matrix Metalloproteinases

Abstract

Cadmium (Cd) is a toxic heavy metal that is found in the environment from both natural and anthropogenic sources. It is a xenobiotic environmental pollutant with no known essential biological functions. Exposure to cadmium has been implicated as a risk factor for cardiovascular disease by inducing inflammation and promoting fibrosis of cardiac tissue. The aim of this study was to evaluate the role of low dose chronic cadmium exposure in modulating cardiac matrix metalloproteinases (MMPs) in the heart of rats. Adult male Sprague-Dawley rats were exposed to 15 ppm CdCl2 in drinking water for 10 weeks followed by withdrawal of cadmium treatment for 4 weeks and their heart tissue were obtained. Inflammatory status in the cardiac tissue was evaluated by real-time PCR while protein expression and enzyme activity of MMP-2, MMP-9 and their endogenous inhibitors (TIMP-1 and TIMP-2) was evaluated by western blotting and gelatin zymography, respectively. Results show that the administered cadmium dose incites an inflammatory response until week 10 that is slightly diminished after 4 weeks. At the protein level, cadmium incites a differential effect on the expression and activity of gelatinases and their endogenous inhibitors in an exposure-dependent manner. In conclusion, the present study provides substantial evidence of cadmium induced imbalance in the MMP-TIMP system in the cardiac tissue. This imbalance may be mediated by cadmium-induced inflammation that could contribute to various cardiovascular pathologies.