Modest effect on plaque progression and vasodilatory function in atherosclerosis-prone mice exposed to nanosized TiO2

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.

Methods

We investigated plaque progression and vasodilatory function in apolipoprotein E knockout ( ApoE ^-/-) mice exposed to TiO ₂. ApoE ^-/-mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO ₂(fTiO ₂, 288 nm), photocatalytic 92/8 anatase/rutile TiO ₂(pTiO ₂, 12 nm), or rutile nano TiO ₂(nTiO ₂, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO ₂(0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO ₂-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).

Results

The exposure to nTiO ₂was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE ^-/- mice exposed to fine and photocatalytic TiO ₂had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO ₂.

Conclusion

Repeated exposure to nanosized TiO ₂particles was associated with modest plaque progression in ApoE ^-/- mice. There were no associations between the pulmonary TiO ₂exposure and inflammation or vasodilatory dysfunction.

Related collections

Most cited references 56

Record: found
Abstract: found
Article: not found

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

Qinghua Sun, Aixia Wang, Ximei Jin … (2005)

Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

0 comments Cited 221 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis.

Nicholas Mills, Håkan Törnqvist, Simon Robinson … (2005)

Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans. In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 microg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 microg/min), sodium nitroprusside (2 to 8 microg/min), and verapamil (10 to 100 microg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%). At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.

0 comments Cited 183 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress.

Constantinos Sioutas, Jesus A Araujo, Michael Kleinman … (2008)

Air pollution is associated with significant adverse health effects, including increased cardiovascular morbidity and mortality. Exposure to particulate matter with an aerodynamic diameter of <2.5 microm (PM(2.5)) increases ischemic cardiovascular events and promotes atherosclerosis. Moreover, there is increasing evidence that the smallest pollutant particles pose the greatest danger because of their high content of organic chemicals and prooxidative potential. To test this hypothesis, we compared the proatherogenic effects of ambient particles of <0.18 microm (ultrafine particles) with particles of <2.5 microm in genetically susceptible (apolipoprotein E-deficient) mice. These animals were exposed to concentrated ultrafine particles, concentrated particles of <2.5 microm, or filtered air in a mobile animal facility close to a Los Angeles freeway. Ultrafine particle-exposed mice exhibited significantly larger early atherosclerotic lesions than mice exposed to PM(2.5) or filtered air. Exposure to ultrafine particles also resulted in an inhibition of the antiinflammatory capacity of plasma high-density lipoprotein and greater systemic oxidative stress as evidenced by a significant increase in hepatic malondialdehyde levels and upregulation of Nrf2-regulated antioxidant genes. We conclude that ultrafine particles concentrate the proatherogenic effects of ambient PM and may constitute a significant cardiovascular risk factor.

0 comments Cited 153 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Part Fibre Toxicol

Title: Particle and Fibre Toxicology

Publisher: BioMed Central

ISSN (Electronic): 1743-8977

Publication date Collection: 2011

Publication date (Electronic): 10 November 2011

Volume: 8

Page: 32

Affiliations

[1 ]Department of Public Health, University of Copenhagen, 1014 Copenhagen K, Denmark

[2 ]Department of Pharmacology and Pharmacotherapy, University of Copenhagen, 2100 Copenhagen Ø, Denmark

[3 ]National Research Centre for the Working Environment, 2100 Copenhagen Ø, Denmark

Article

Publisher ID: 1743-8977-8-32

DOI: 10.1186/1743-8977-8-32

PMC ID: 3245428

PubMed ID: 22074227

SO-VID: 0fa5195b-668e-48de-9b7a-42de7fecf794

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.