Nanoparticle inhalation enhances cardiac protein phosphorylation and neurotransmitter synthesis in the nodose ganglia of rats.
Kan H; Wu Z; Young S; Chen TB; Cumpston JL; Chen F; Castranova V
Toxicologist 2011 Mar; 120(Suppl 2):313
Growing evidence from epidemiological studies indicates that an increase of the small sized particle, particularly nanoparticle, component in ambient air is strongly associated with increased incidence of cardiovascular diseases. Animal studies demonstrated that pulmonary inhalation of nanoparticles stimulates the development of atherosclerosis and impairs vascular function. However, the effect of inhaled nanoparticles on cardiac muscle has not been reported. The present study investigated the effect of ultrafine titanium dioxide (UFTiO2) on the heart. We found that direct exposure of rat cardiac myocytes in vitro to UFTiO2 (1 mu g/ml) for 4 hrs did not alter myocyte contractility, calcium handling, or the phosphorylation level of cardiac proteins, such as p38 mitogen-activated protein kinase (p38 MAPK) and cardiac troponin I (cTnI). In contrast, pulmonary inhalation of UFTiO2 (6 mg/m3) for 4 hrs significantly increased the phosphorylation status of p38 MAPK and cardiac cTnI in the heart. In addition, pulmonary exposure to UFTiO2 also increased neurotransmitter substance P synthesis in nodose ganglia, which is involved in the integration and control of lung and heart function. However, neither mRNA expression nor protein synthesis of TNF-alpha, IL-1 and IL- 6 was detected in the heart or peripheral blood respectively. Blood cell counts and differentials did not indicate significant systemic inflammation. Our results suggested that pulmonary exposure to UFTiO2-enhanced the phosphorylation level of p38 MAPK and cTnI in cardiac tissue. Such responses may contribute to cardiac dysfunction which is independent of the direct interaction of UFTiO2 with the heart or systemic inflammation, but may involve a lung-neuron-regulated pathway.
Airborne-particles; Biohazards; Biological-effects; Cardiopulmonary-system; Cardiopulmonary-system-disorders; Cardiovascular-disease; Cardiovascular-system; Cardiovascular-system-disease; Cardiovascular-system-disorders; Cellular-reactions; Epidemiology; Exposure-levels; Inhalation-studies; Laboratory-animals; Lung-disorders; Lung-irritants; Nanotechnology; Particulates; Physiological-effects; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC