Nickel and Disrupted Endothelial Integrity: Implications to PM2.5-associated Cardiovascular Disorders

Abstract

S-30A2-4 Background/Aims: It has been well documented that exposure to ambient fine particulate matter (PM2.5) induces increased risks for cardiovascular disorders (CVD) in humans. However, the mechanism(s) and component(s) responsible for PM2.5-associated CVD are still poorly understood. This study was conducted to test the hypothesis that nickel (Ni) plays critical roles in PM2.5-associated CVD. Methods: To test this hypothesis, we identified 2 areas, Jinchang and Zhangye, in China with comparable PM2.5, but different Ni exposures. In all, 30 healthy nonsmoking female subjects aged between 60 and 65 were recruited from each area to measure the following: (1) CVD risk biomarkers [C-reactive protein, MCP-1, IL-6, ICAM-1, and VCAM-1]; (2) markers of vascular integrity (intima-media thickness [IMT] of carotid artery); and (3) vascular endothelial repair marker (circulating endothelial progenitor cells [CEPCs]). Results: The ambient concentrations of PM2.5 were 43.0 ± 40.7 and 45.5 ± 47.7 μg/m3 in Jinchang and Zhangye, respectively, with no significant difference. However, the ambient level of Ni in Jinchang (204.8 ± 268.6 ng/m3) was approximately 76-fold higher than that in Zhangye (2.7 ± 4.3 ng/m3). No differences were detected between the 2 groups of recruited subjects in age, body mass index, blood pressure, and lipid profiles. All CVD risk markers, except ICAM-1, were higher in subjects from Jinchang as compared with those from Zhangye; and significant differences in C-reactive protein and IL-6 were detected between the 2 groups. The IMT measured by B-mode ultrasound imaging was significantly thicker in subjects recruited from Jinchang than that in those from Zhangye. CEPCs, enumerated by flow cytometry, were significantly lower in subjects recruited from Jinchang than that in those from Zhangye. Correlation analyses further indicated that IMT correlated negatively with the number of CEPCs while positively with MCP-1. Conclusion: These results may suggest the following: (1) Ni is an important component responsible for PM2.5-induced cardiovascular effects; (2) the reduced capacity of vascular endothelial repair may partially explain the critical roles of Ni in PM2.5-associated CVD.