Issue 5, 2015

Respiratory exposure to single-walled carbon nanotubes induced changes in vascular homeostasis and the expression of peripheral blood related genes in a rat model

Abstract

Epidemiological studies have demonstrated that nanometre particles in polluted air can increase the risk of CVD, which is dangerous to mankind. However, little is known regarding the indirect toxic effects on the cardiovascular system of respiratory tract exposure to nanometre particles. As a typical nanomaterial, SWCNTs have gained enormous popularity because of their unique properties. However, increasing attention has been paid to the potential pulmonary toxic effects of respiratory tract exposure to SWCNT than to the potential link of this exposure to cardiovascular disease risk. In this study, a rat intratracheal instillation model was used to evaluate the systemic and secondary effects of respiratory tract exposure to SWCNT, specifically changes in lung tissues, the circulatory system and vascular function. We found increased levels of inflammatory factors and interstitial inflammation in the lungs in this rat model. In addition, up-regulated levels of cytokines and an increase in white blood cells, platelets and fibrinogen were detected in the plasma. These changes were followed by increased blood viscosity in the high dose SWCNT exposure group. In addition, damage to the ultrastructure of the vascular intima in the rats was observed. Changes in coagulation and fibrinolysis activating factors were detected in the plasma. Lower expression of t-PA and higher expression of vWF were observed in the vascular intima of rats exposed to SWCNT at 10.5 and 17.5 mg per kg b.w. for 30 days and 60 days. After exposure to SWCNT for 60 days at 17.5 mg per kg b.w., decreased expression of t-PA gene and increased expression of TM, p38MAPK and PAI-1 genes were observed in the peripheral blood of the rats. Based on these results, we conclude that cardiovascular toxicity caused by respiratory tract exposure to SWCNTs may be induced by indirect effects on vascular homeostasis, which is different from previously reported direct cardiac effects of SWCNT. The present work established a correlation between pulmonary changes and CVD following pulmonary exposure to SWCNT. This study indicates a possible pathophysiological mechanism for CVD caused by pulmonary exposure to SWCNT. More importantly, these results supplement toxicological evaluation data for the risk of CVD caused by respiratory tract exposure to SWCNT.

Graphical abstract: Respiratory exposure to single-walled carbon nanotubes induced changes in vascular homeostasis and the expression of peripheral blood related genes in a rat model

Article information

Article type
Paper
Submitted
15 Feb 2015
Accepted
31 May 2015
First published
01 Jun 2015

Toxicol. Res., 2015,4, 1225-1237

Author version available

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