ABSTRACT
Chronic exposure to arsenic is associated with the increasing risk of morbidity and mortality from cardiovascular diseases (CVDs). However, underlying mechanisms of arsenic-related CVDs has not yet been clearly understood. Endothelial dysfunction plays a central role in the development of atherosclerosis leading to CVDs. We hypothesized that endothelial damage or dysfunction is an early event of arsenic-related CVDs. Soluble thrombomodulin (sTM) in the serum is thought to be a specific marker for endothelial damage or dysfunction. To evaluate the effects of arsenic exposure on endothelial dysfunction, we conducted a population based study recruiting human subjects from arsenic-endemic and non-endemic areas in Bangladesh. We observed that subjects’ arsenic exposure levels had significant positive associations with serum sTM levels. Serum sTM levels were higher in the higher exposure gradients of arsenic exposure if we stratified the subjects into three groups (low, medium and high) based on the arsenic concentrations of the subjects' drinking water, hair and nails. In another study conducted almost on the same population, it was observed that chronic exposure to arsenic significantly increased the levels of plasma Big-ET-1, a precursor form of endothelin-1 which has been recognized as a potent vasoconstrictor and a marker of endothelial dysfunction. Interestingly, we observed that sTM and plasma Big-ET-1 levels were significantly higher in the hypertensive groups compared to the normotensive counterpart of the study subjects in arsenic-endemic areas. Taken together our results suggest that chronic exposure to arsenic causes endothelial dysfunction which may be a potential mechanism of arsenic-related hypertension or other forms of CVDs.
