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Vascular and thrombogenic effects of pulmonary exposure to libby amphibole.
MedLine Citation:
PMID:  22352330     Owner:  NLM     Status:  In-Data-Review    
Exposure to Libby amphibole (LA) asbestos is associated with increased incidences of human autoimmune disease and mortality related to cardiovascular diseases. However, the systemic and vascular impacts are less well examined because of the dominance of pulmonary disease. It was postulated that regardless of the type of exposure scenario, LA exposure might produce systemic and vascular inflammogenic and thrombotic alterations in healthy and cardiovascular compromised rat models. Samples from three independent studies were examined. In the first study, male Wistar Kyoto (WKY), spontaneously hypertensive (SH), and SH heart failure (SHHF) rats were intratracheally instilled once with 0 (vehicle), 0.25, or 1 mg/rat of LA. In the second study, F344 rats were instilled with vehicle or LA at 0.5, 1.5, or 5 mg/rat. In the third study, F344 rats were instilled with the same mass concentrations of LA delivered by biweekly multiple instillations over 3 mo to simulate an episodic subchronic exposure. Complete blood count, platelet aggregation, serum cytokines, and biomarkers of systemic and aortic effects were examined. LA reduced adenosine diphosphate (ADP)-induced platelet aggregation and decreased circulating platelets in WKY (1 mg/rat) and F344 (5 mg/rat) at the 3-mo time point but did not do so in SH or SHHF rats. A decline in circulating lymphocytes with age appeared to be exacerbated by LA exposure in F344 rats but the differences were not significant. Aorta mRNA expression for biomarkers of oxidative stress (HO-1, LOX-1), inflammation (MIP-2), and thrombosis (tPA, PAI-1, vWf) were increased at baseline in SH and SHHF relative to WKY. LA exposure upregulated several of these biomarkers and also those involved in aortic contractility of WKY rats at 3 mo, suggesting thrombogenic, vasocontractile, and oxidative stress-mediated impairments. The aorta changes in F344 rats were less remarkable than changes noted in WKY following LA exposure. In conclusion, exposure to LA decreased circulating platelets and platelet coagulability while increasing the expression of oxidative stress, thrombosis, and vasoconstriction biomarkers in the aorta of healthy rats. These changes were similar to those noted at baseline in SH and SHHF rats, suggesting that LA-induced pulmonary injury might increase the risk of developing cardiovascular disease in healthy individuals.
J H Shannahan; M C Schladweiler; R F Thomas; W O Ward; A J Ghio; S H Gavett; U P Kodavanti
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of toxicology and environmental health. Part A     Volume:  75     ISSN:  1528-7394     ISO Abbreviation:  J. Toxicol. Environ. Health Part A     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100960995     Medline TA:  J Toxicol Environ Health A     Country:  England    
Other Details:
Languages:  eng     Pagination:  213-31     Citation Subset:  IM    
a Curriculum in Toxicology, UNC School of Medicine , Chapel Hill , North Carolina , USA.
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