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

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.

<p>Zinc Oxide Nanoparticles Induce Mitochondrial Biogenesis Impairment and Cardiac Dysfunction in Human iPSC-Derived Cardiomyocytes</p>

“…12 Similarly, by using an in vitro gas-blood barrier model, it has been reported that ZnO NPs can induce detrimental effects via the lungs into the cardiovascular system. 13,14 ZnO NPs were also found to negatively impact cardiorespiratory function and energy metabolism in freshwater fish (Catostomus commersonii). 15 Many in vitro studies revealed that ZnO NPs can induce toxic effects in cardiac cells such as a decrease in survival rate, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and release of inflammatory factors.…”

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

“…An important consideration is the Zn source. We chose to use ZnSO 4 as many Zn supplements provide Zn as ZnSO 4 , and several comparative animal studies used ZnSO 4 . However, it is possible that other Zn sources such as Zn gluconate or Zn oxide may lead to different effects, and thus, should be explored.…”

Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome

“…We have reported that pulmonary and systemic microvascular inflammation [ 29 , 32 ] follow ENM inhalation exposure. Consistent with this, other systemic morbidities known to follow pulmonary ENM exposures include: inflammation/apoptosis [ 8 , 9 ], macrovascular and microvascular dysfunction [ 10 ], atherogenesis [ 11 ], and organ level ischemia [ 12 ]. The developing fetus is equally a systemic target of numerous anthropogenic toxicants [ 13 ].…”