Vascular and Thrombogenic Effects of Pulmonary Exposure to Libby Amphibole

Abstract

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.

Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

“…Increased leukocyte rolling and adherence (Nurkiewicz et al, 2006), increased reactive species production (Nurkiewicz et al, 2009; LeBlanc et al, 2010) leading to reduced NO bioavailability (Nurkiewicz et al, 2009; Minarchick et al, 2015) that subsequently impairs normal vascular function has been well described in the cardiovascular toxicology literature, by our group and others (Channell et al 2012; Vedal et al 2013; Wingard et al, 2011; Shannahan et al, 2012). Because systemic dependence on NO signaling increases dramatically for numerous processes during pregnancy (Thompson and Weiner, 2001; Ni et al, 1997; Mandala et al, 2002), it is vital to identify any potential vascular sensitivities or dysfunction prior to conception to prevent possible health complications or pregnancy loss.…”

Manufactured and airborne nanoparticle cardiopulmonary interactions: a review of mechanisms and the possible contribution of mast cells

“…Additionally, mice exposed to PM collected in Dusseldorf, Germany demonstrated a reduced bleeding time which was dependent on IL-6 release from the lung (Mutlu et al 2007). Amphibole asbestos fibers, which are extremely biopersistent within the lung, have demonstrated acute systemic effects including acute changes in platelet activity, and an acute phase response in rats possibly via the release of proinflammatory cytokines and/or oxidatively-modified proteins (Shannahan et al 2012a in press, Shannahan et al 2012b in press). Since the quantities of leachable and thus translocatable components in these studies are most likely biologically insignificant, these studies provide evidence that particles do not have to translocate to cause systemic effects.…”

Naturally Occurring Asbestos: Potential for Human Exposure, Southern Nevada, USA

“…Examples include the amphibole minerals winchite, magnesioriebeckite, and richterite from studies in Libby, MT (e.g., Meeker et al, 2003;Shannahan et al, 2012), erionite (a zeolite mineral) in Turkey and North Dakota (Carbone et al, 2011;Ryan et al, 2011), and antigorite (a serpentine mineral) in Poland (Wozniak et al, 1988) and New Caledonia (Baumann et al, 2010). Toxicity is related to the width, length, aspect ratio, surface area, and surface chemical composition of the mineral fiber (Aust et al, 2011).…”