Association between Arsenic Exposure from Drinking Water and Plasma Levels of Soluble Cell Adhesion Molecules

Inorganic arsenic is a natural element of the earth crust. It enters drinking water supplies from natural deposits or from agricultural and industrial practices. Long-term exposure to arsenic in groundwater has been related to elevated risks of cancer of the bladder, lungs, skin, kidneys, and liver (Chen CJ et al. 1988; Chen CL et al. 2004; Morales et al. 2000; Tseng WP 1989); diabetes (Tseng CH et al. 2002; Wang SL et al. 2003); cardiovascular disease (CVD) (Chen CJ et al. 1995, 1996; Chiou et al. 1997; Tseng CH et al. 2003; Wang CH et al. 2002); adverse pregnancy outcomes (Ahmad et al. 2001; von Ehrenstein et al. 2006); and a decrease in children’s intellectual function (von Ehrenstein et al. 2007; Wasserman et al. 2004). Evidence of high-level arsenic exposure (> 200 μg/L) on vascular disease is largely based on a series of epidemiologic studies in southwestern Taiwan (Ch’i and Blackwell 1968; Chen CJ et al. 1996; Chiou et al. 1997; Tseng CH et al. 2003; Wang CH et al. 2002), collectively suggesting that arsenic exposure induces atherosclerosis, the most common pathologic process underlying CVD that often manifests clinically as coronary disease, stroke, or peripheral arterial disease. However, neither a biological mechanism nor the effect of low-level exposure is clear. More recently, in a cross-sectional analysis, we found a positive association between arsenic exposure and high pulse pressure (Chen Y et al. 2006a), an indicator of arterial stiffness that is associated with an increased risk of atherosclerosis (Dart and Kingwell 2001; Safar et al. 2003). Prospective studies of CVD risk factors, biomarkers, and clinical end points in populations exposed to a wide range of arsenic levels are therefore a public health research priority. Experimental studies have suggested that arsenic increases the production of reactive oxygen species such as hydrogen peroxide (Barchowsky et al. 1999; Chen YC et al. 1998) and hydroxyl radicals (Wang TS et al. 1996), which may then lead to oxidative stress. In turn, arsenic-induced oxidative stress may mediate gene expression, inflammatory responses, or impaired nitric oxide homeostasis (Simeonova and Luster 2004). These events may ultimately lead to endothelial dysfunction, which disrupts the balance in vasomotor tone between relaxation and contraction and increases the risk for vascular diseases such as hypertension and atherosclerosis (Kumagai and Pi 2004). Circulating markers of systemic inflammation and endothelial dysfunction, such as soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular adhesion molecule-1 (sVCAM-1) have been shown to predict future CVD (Blankenberg et al. 2001; Hwang et al. 1997; Ridker et al. 1998, 2000). Expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells was higher in cells stimulated with arsenic than in those without arsenic (Hou et al. 2005). Treatment of mice with arsenic trioxide was associated with a clear increase in expression of ICAM-1 and VCAM-1 (Griffin et al. 2000). However, epidemiologic studies are needed to examine these associations in human populations exposed to arsenic at doses relevant to environmental levels of arsenic exposure. We evaluated the effects of arsenic exposure on plasma levels of sICAM-1 and sVCAM-1 among 115 individuals participating in a 2 × 2 randomized, placebo-controlled, double-blind trial of vitamin E and selenium supplementation in Araihazar, Bangladesh. Because of the availability of plasma and urine samples at baseline and at follow-up, we were also able to evaluate the effects of changes in arsenic exposure, as well as the effects of vitamin E and selenium supplementation, on changes in plasma sICAM-1 and sVCAM-1.