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International audience; Nanoparticles (NPs) are widely used in food, and analysis of their potential gastrointestinal toxicity is necessary. The present study was designed to determine the effects of silica dioxide (SiO2), titanium dioxide (TiO2), and zinc oxide (ZnO) NPs on cultured THP-1 monocyte-derived macrophages and human epithelial colorectal adenocarcinoma (Caco-2) cells. Exposure to ZnO NPs for 24 h increased the production of redox response species (ROS) and reduced cell viability in a dose-dependent manner in THP-1 macrophages and Caco-2 cells. Although TiO2 and SiO2 NPs induced oxidative stress, they showed no apparent cytotoxicity against both cell types. The effects of functionalized SiO2 NPs on undifferentiated and differentiated Caco-2 cells were investigated using fluorescently labeled SiO2 NPs with neutral, positive, or negative surface charge. Exposure of both types of cells to the three kinds of SiO2 NPs significantly increased their interaction in a dose-dependent manner. The largest interaction with both types of cells was noted with exposure to more negatively surface-charged SiO2 NPs. Exposure to either positively or negatively, but not neutrally, surface-charged SiO2 NPs increased NO levels in differentiated Caco-2 cells. Exposure of differentiated Caco-2 cells to positively or negatively surface-charged SiO2 NPs also upregulated interleukin-8 expression. We conclude that functionalized surface-charged SiO2 NPs can induce pro-inflammatory responses but are noncytotoxic.

Aryl hydrocarbon receptor (AHR) is a transcription factor that binds to DNA as a heterodimer with the AHR nuclear translocator (ARNT) after interaction with ligands, such as polycyclic and halogenated aromatic hydrocarbons and other xenobiotics. The endogenous ligands and functions of AHR have been the subject of many investigations. In the present study, the potential role of AHR signaling in the development of left ventricular hypertrophy and cardiac fibrosis by angiotensin II (Ang II) infusion was investigated in mice lacking the AHR gene (Ahr(−/−)). We also assessed the hypothesis that fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, reduces cardiac fibrosis through the c-Jun signaling. Male Ahr(−/−) and age-matched wild-type mice (n = 8 per group) were infused with Ang II at 100 ng/kg/min daily for 2 weeks. Treatment with Ang II increased systolic blood pressure to comparable levels in Ahr(−/−) and wild-type mice. However, Ahr(−/−) mice developed severe cardiac fibrosis after Ang II infusion compared with wild-type mice. Ang II infusion also significantly increased the expression of endothelin in the left ventricles of Ahr(−/−) mice, but not in wild-type mice, and significantly increased the c-Jun signaling in Ahr(−/−) mice. Ang II infusion also significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and the downstream target vascular endothelial growth factor (VEGF) in the left ventricles of Ahr(−/−) mice. These results suggested pathogenic roles for the AHR signaling pathway in the development of cardiac fibrosis. Treatment with fenofibrate reduced cardiac fibrosis and abrogated the effects of Ang II on the expression of endothelin, HIF-1α, and VEGF. The inhibitory effect of fenofibrate on cardiac fibrosis was mediated by suppression of VEGF expression through modulation of c-Jun/HIF-1α signaling.

PM2.5 is a particle with a diameter

Smoking increases the risk of atherosclerosis-related events, such as myocardial infarction and ischemic stroke. Recent studies have examined the expression levels of altered microRNAs (miRNAs) in various diseases. The profiles of tissue miRNAs can be potentially used in diagnosis or prognosis. However, there are limited studies on miRNAs following exposure to cigarette smoke (CS). The present study was designed to dissect the effects and cellular/molecular mechanisms of CS-induced atherosclerogenesis. Apolipoprotein E knockout (ApoE KO) mice were exposed to CS for five days a week for two months at low (two puffs/min for 40 min/day) or high dose (two puffs/min for 120 min/day). We measured the area of atherosclerotic plaques in the aorta, representing the expression of miRNAs after the exposure period. Two-month exposure to the high dose of CS significantly increased the plaque area in aortic arch, and significantly upregulated the expression of atherosclerotic markers (VCAM-1, ICAM-1, MCP1, p22phox, and gp91phox). Exposure to the high dose of CS also significantly upregulated the miRNA-155 level in the aortic tissues of ApoE KO mice. Moreover, the expression level of miR-126 tended to be downregulated and that of miR-21 tended to be upregulated in ApoE KO mice exposed to the high dose of CS, albeit statistically insignificant. The results suggest that CS induces atherosclerosis through increased vascular inflammation and NADPH oxidase expression and also emphasize the importance of miRNAs in the pathogenesis of CS-induced atherosclerosis. Our findings provide evidence for miRNAs as potential mediators of inflammation and atherosclerosis induced by CS.

Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO2 and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO2 particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation.

Background The use of carbon nanotubes has increased lately. However, the cardiovascular effect of exposure to carbon nanotubes remains elusive. The present study investigated the effects of pulmonary exposure to single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs) on atherosclerogenesis using normal human aortic endothelial cells (HAECs) and apolipoprotein E-deficient (ApoE−/−) mice, a model of human atherosclerosis. Methods HAECs were cultured and exposed to SWCNTs or DWCNTs for 16 h. ApoE−/− mice were exposed to SWCNTs or DWCNTs (10 or 40 μg/mouse) once every other week for 10 weeks by pharyngeal aspiration. Results Exposure to CNTs increased the expression level of adhesion molecule (ICAM-1) and enhanced THP-1 monocyte adhesion to HAECs. ApoE−/− mice exposed to CNTs showed increased plaque area in the aorta by oil red O staining and up-regulation of ICAM-1 expression in the aorta, compared with vehicle-treated ApoE−/− mice. Endothelial progenitor cells (EPCs) are mobilized from the bone marrow into the circulation and subsequently migrate to the site of endothelial damage and repair. Exposure of ApoE−/− mice to high-dose SWCNTs or DWCNTs reduced the colony-forming units of EPCs in the bone marrow and diminished their migration function. Conclusion The results suggested that SWCNTs and DWCNTs enhanced atherosclerogenesis by promoting monocyte adhesion to endothelial cells and inducing EPC dysfunction. Electronic supplementary material The online version of this article (doi:10.1186/s12989-016-0166-0) contains supplementary material, which is available to authorized users.

Nanomaterials tend to agglomerate in aqueous media, resulting in inaccurate safety assessment of the biological response to these substances. The present study searched for suitable dispersion methods for the preparation of nanomaterial suspensions. Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles were dispersed in a biocompatible dispersion medium by direct probe-type sonicator and indirect cup-type sonicator. Size characterization was completed using dynamic light scattering and transmission electron microscopy. A series of dispersion time and out- put power, as well as two different particle concentrations were tested. Microscopic contamination of metal titanium that broke away from the tip of the probe into the suspension was found. Size of agglomerated nanoparticles decreased with increase in sonication time or output power. Particle concentration did not show obvious effect on size distribution of TiO2 nanoparticles, while signifi- cant reduction of secondary diameter of ZnO was observed at higher concentration. A practicable protocol was then adopted and sizes of well-dispersed nanoparticles increased by less than 10% at 7 d after sonication. Multi-walled carbon nanotubes were also well dispersed by the same protocol. The cup-type sonicator might be a useful alternative to the traditional bath-type sonicator or probe- type sonicator based on its effective energy delivery and assurance of suspension purity.

Titanium dioxide (TiO2) nanoparticles are widely used in cosmetics, sunscreens, biomedicine, and food products. When used as a food additive, TiO2 nanoparticles are used in significant amounts as white food-coloring agents. However, the effects of TiO2 nanoparticles on the gastrointestinal tract remain unclear. The present study was designed to determine the effects of five TiO2 particles of different crystal structures and sizes in human epithelial colorectal adenocarcinoma (Caco-2) cells and THP-1 monocyte-derived macrophages. Twenty-four-hour exposure to anatase (primary particle size: 50 and 100 nm) and rutile (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner in THP-1 macrophages, but in not Caco-2 cells. However, 72-h exposure of Caco-2 cells to anatase (50 nm) TiO2 particles reduced cellular viability in a dose-dependent manner. The highest dose (50 µg/mL) of anatase (100 nm), rutile (50 nm), and P25 TiO2 particles also reduced cellular viability in Caco-2 cells. The production of reactive oxygen species tended to increase in both types of cells, irrespective of the type of TiO2 particle. Exposure of THP-1 macrophages to 50 µg/mL of anatase (50 nm) TiO2 particles increased interleukin (IL)-1β expression level, and exposure of Caco-2 cells to 50 µg/mL of anatase (50 nm) TiO2 particles also increased IL-8 expression. The results indicated that anatase TiO2 nanoparticles induced inflammatory responses compared with other TiO2 particles. Further studies are required to determine the in vivo relevance of these findings to avoid the hazards of ingested particles.

Effects of SWCNTs and DWCNTs on cell viability. (PPTX 70 kb)

Zinc oxide (ZnO) nanoparticles have been widely used in industry, cosmetics, and biomedicine. Recent studies suggested that these nanoparticles could have a major impact on the cardiovascular system. Endothelial progenitor cells (EPCs) contribute to postnatal endothelial repair and regeneration. The present study dissected the effects of ZnO nanoparticles on vasculogenesis using human endothelial colony forming cells (ECFCs), which participate in post-natal vasculogenesis. Two types of ZnO particles were used (nano and micro), in addition to zinc chloride solutions with zinc ion concentrations equal to those in ZnO nanoparticles. Twenty-four-hour exposure induced cytotoxicity in a dose-dependent manner and increased ECFCs apoptosis in all groups. The exposure also reduced the functional capacity of ECFCs on Matrix gel to form tubules, compared with the control cells. These effects were associated with downregulation of expression of vascular endothelial growth factor receptor, VEGFR2 and CXC chemokine receptor, CXCR4. The results suggest that ZnO nanoparticles suppress vasculogenesis from ECFCs through downregulation of the expression of receptors related to vasculogenesis. These effects are based the concentration of released Zn(II).