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Systemic and Vascular Alterations in Healthy and Cardiovascular Compromised Rats Exposed to Libby Amphibole
Citation:
KODAVANTI, U. P., R. Thomas, J. Shannahan, M. SCHLADWEILER, S. H. GAVETT, AND D. Carlin. Systemic and Vascular Alterations in Healthy and Cardiovascular Compromised Rats Exposed to Libby Amphibole. Presented at American Thoracic Society (ATS) Meeting, Denver, CO, May 13 - 18, 2010.
Impact/Purpose:
This abstract examined effects of Libby amphibole asbestos induced vascular changes in the aorta and in the blood. It shows that there are coagulative effects and aortic biomarker changes after long duration in the Libby amphibole exposed animals.
Description:
Rationale: Acute pulmonary injury and chronic disease can impact systemic vasculature because the lung capillary network can release inflammogenic and vasoactive mediators into the circulation. Occupational exposure to Libby amphibole (LA) type asbestos is associated with increased human cardiovascular mortality and autoimmune disease. We hypothesized that LA exposure will cause systemic and vascular alterations through increased expression of receptors that recognize circulating oxidatively modified lipids (LOX-I) and proteins (RAGE) in healthy and cardiovascular compromised rats. Methods: Healthy male Wistar Kyoto (WKY), spontaneously hypertensive (SH) and SH heart failure (SHHF) rats were intratracheally instilled once with either saline or LA at 0.25 or 1.0 mg/rat, or F344 rats with saline or LA at 0.5, 1.5 or 5.0 mg/rat. Three months later CBC and platelet aggregation were analyzed along with ITIRNA expression of disease biomarkers in the aorta. Results: We observed that LA exposure was associated with reduced ADP-induced platelet aggregation and decreased circulating platelets in WKY (l mg/rat) and F344 (5 mg/rat) but not SH or SHHF rats. A general decline in circulating lymphocytes with age was slightly exacerbated by LA exposure in F344 rats. Aorta mRNA expression for biomarkers of oxidative stress (HO-1), inflammation (MIP2), and thrombosis (tPA, PAl-I, vWf) were increased at baseline in SH and SHHF relative to WKY. LOX-1 mRNA was also highly upregulated at baseline in SH and SHHF when compared to WKY rats. LA exposure upregulated HO-1, ET-1, ETR-A, TIMP-2, TF, tPA, PAl-I, and vWfmRNA along with LOX-1 in the aorta of WKY rats without further increasing the levels in SH and SHHF. The aorta changes in F344 rats were less remarkable than changes noted in WKY following LA exposure. 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 but not cardiovascular compromised rats. Especially with aorta biomarkers, the LA exposure caused healthy rats to appear more like hypertensive rats. These data suggest that LA exposure might increase the risk of developing cardiovascular disease in healthy individuals by increased LOX-1 receptor signaling. (This abstract does not reflect US EPA policy).