Zinc oxide nanoparticle-induced atherosclerotic alterations in vitro and in vivo

Abstract

Zhen Yan,1,* Wenjun Wang,2,* Yongjun Wu,1,* Wei Wang,2 Bing Li,1 Ning Liang,1 Weidong Wu3 1College of Public Health, Zhengzhou University, Zhengzhou, 2School of Public Health, Jining Medical University, Jining, 3School of Public Health, Xinxiang Medical University, Xinxiang, People’s Republic of China *These authors contributed equally to this work Abstract: Engineered zinc oxide nanoparticles (ZnO-NPs) are currently being produced in high tonnage. Exposure to ZnO-NPs presents potential risks to cardiovascular system. Thus far, the toxicological effects of ZnO-NPs on cardiovascular system have not been well characterized. In this study, human coronary artery endothelial cells (HCAECs) were exposed to ZnO-NPs directly or indirectly using a transwell coculture system with human alveolar epithelial cell line A549 to mimic the lung/circulation interaction. It was shown that levels of proinflammatory mediators (interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) and biomarkers of atherosclerogenesis (heme oxygenase-1 [HO-1] and platelet endothelial cell adhesion molecules-1 [PECAM-1]) in the supernatants of culture media were significantly increased. Pretreatment of A549 cells on the apical side of the coculture system with the phagocytosis inhibitor cytochalasin B (CB) blocked ZnO-NP-induced HO-1 and PECAM-1 expression in HCAEC, indicating that endocytosis of ZnO-NPs by alveolar epithelial cells was involved in ZnO-NP-induced HO-1 or PECAM-1 expression in endothelial cells. Moreover, Wistar rats were intratracheally instilled with ZnO-NP suspension and high fat diet (positive control). ZnO-NP treatment induced lung and systemic inflammation, dyslipidemia, increased levels of serum HO-1 and PECAM-1, and aortic pathological damage. Taken together, exposure to ZnO-NPs could induce atherosclerotic alterations, which might involve phagocytosis of nanoparticles and inflammation in the lung. Keywords: zinc oxide nanoparticles, atherosclerosis, lung inflammation, heme oxygenase-1, platelet endothelial cell adhesion molecules-1 

Keywords

• Zinc oxide nanoparticles
• atherosclerosis
• lung inflammation
• heme oxygenase-1
• platelet endothelial cell adhesion molecules-1