EPA Science Inventory

VASCULAR AND THROMBOGENIC EFFECTS OF PULMONARY EXPOSURE TO LIBBY AMPHIBOLE

Citation:

Shannahan, J., M. SCHLADWEILER, R. F. Thomas, B. D. Vallant, W. O. Ward, A. J. GHIO, S. H. GAVETT, U. P. KODAVANTI, AND U. P. KODAVANTI. VASCULAR AND THROMBOGENIC EFFECTS OF PULMONARY EXPOSURE TO LIBBY AMPHIBOLE. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. Taylor & Francis, Inc., Philadelphia, PA, 74(4):213-31, (2012).

Description:

Acute pulmonary injury and chronic disease can impact the systemic vasculature through the release of inflammogenic and vasoactive mediators from the lung into the circulation. Exposure to Libby amphibole (LA) asbestos is associated with increased human cardiovascular mortality and autoimmune disease. We hypothesized that LA exposure will cause systemic and vascular pro-inflammatory and pro-thrombotic alterations in healthy and cardiovascular compromised rats. Male Wistar Kyoto (WKY), spontaneously hypertensive (SH) and SH heart failure (SHHF) rats were intratracheally instilled once 0.0, 0.25 or 1.0 mg/rat of LA, or F344 rats with saline or LA at 0.5, 1.5 or 5.0 mg/rat. F344 rats were also instilled with the same mass concentrations ofLA delivered by multiple instillations over 3 months. Complete blood count, cytokines, platelet aggregation and mRNA expression ofaorta biomarkers were analyzed. LA reduced adenosine diphosphate (ADP)-induced platelet aggregation and decreased circulating platelets in WKY (l mg/rat) and F344 (5 mg/rat) at 3 months time point but not in 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-I, LOX-I), inflammation (MIP-2), and thrombosis (tPA, PAl-I, vWt) were increased at baseline in SH and SHHF relative to WKY. LA exposure upregulated LOX-I, HO-I, ET-I, ETR-A, TIMP-2, TF, tPA, PAl-I, and vWf mRNA in the aorta of WKY rats at 3 months. These markers were upregulated at baseline in control SH and SHHF. 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 ofoxidative stress, thrombosis and vasoconstriction biomarkers in the aorta ofhealthy rats. These changes were similar to baseline values in SH and SHHF. These data suggest that LA exposure might increase the risk of microvascular thrombosis and vascular disease in healthy individuals.

Purpose/Objective:

We demonstrate that healthy rats develop small degree of vascular complications as a result of chronic inflammation induced by Libby amphibole exposure. These data support the recent epidemiology of Libby region showing association between Libby amphibole exposure and increases in mortality due to cardiovascular cause.

URLs/Downloads:

JOURNAL OF TOXICOLOGICAL AND ENVIRONMENTAL HEALTH A   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Start Date: 02/21/2012
Completion Date: 02/21/2012
Record Last Revised: 10/29/2012
Record Created: 02/03/2012
Record Released: 02/03/2012
OMB Category: Other
Record ID: 241086

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH