Citation:

Farraj, A., J. Shanahan, L. Thompson, C. Perez, N. Coates, C. King, M. Hazari, AND J. Brown. Serum from Diesel Exhaust-Exposed Rats with Cardiac Dysfunction Alters Aortic Endothelial Cell Function In Vitro: Circulating Mediators as Causative Factors? Society of Toxicology, New Orleans, LA, March 13 - 17, 2016.

Impact/Purpose:

This work helps shed light on the uncertainty with respect to the mechanisms that mediate cardiovascular dysfunction after exposure to air pollution. This work suggests that cardiac effects in particular may potentially be driven by circulating soluble mediators of inflammation that target the heart and/or vasculature. These findings provide biological plausibility to the epidemiological evidence linking short and long term exposure to air pollution to increased cardiovascular morbidity and mortality.

Description:

Although circulating inflammatory mediators are strongly associated with adverse cardiovascular outcomes triggered by inhaled air pollution, direct cause-effect linkage has not been established. Given that endothelial toxicity often precedes and precipitates cardiac dysfunction, the purpose of this study was to examine the plausibility of serum bound factors as drivers of both endothelial toxicity and cardiac effects. We hypothesized that serum taken from diesel exhaust (DE)-exposed rats that later develop cardiac dysfunction would alter aortic endothelial cell function in vitro. To assess cardiac function in vivo, left ventricular pressure assessments were conducted in spontaneously hypertensive rats one day after a single 4 hour whole body exposure to 150 or 500 u/m3 DE or filtered air. Rat aortic endothelial cells (RAEC) were then exposed to diluted serum collected 1 hour after exposure from a separate cohort of similarly exposed rats for measures of VCAM-1, cell viability, nitric oxide synthase levels, and mRNA expression of key mediators of inflammation. Exposure of rats to either 150 or 500 u/m3 DE decreased end systolic pressure and left ventricular pressure, consistent with a decrease in mean arterial pressure. Treatment of naïve RAECs to serum from rats exposed to 500 u/m3 DE caused an increase in the cell surface marker VCAM-1 and a decrease in the expression of ALOX15 mRNA relative to cells treated with serum from rats exposed to filtered air. Serum from rats exposed to either 150 or 500 u/m3 DE caused a decrease in cell viability and nitric oxide synthase production in RAECs relative to cells treated with serum from rats exposed to filtered air. Proteomic assessments of rat sera are currently being conducted to identify circulating mediators with altered expression after DE exposure. These results suggest that increases in circulating inflammatory mediators may contribute to the cardiac pathophysiology caused by exposure to air pollution (This abstract does not reflect EPA policy; supported in part by NIH R01 ES019311 and K99 ES024392).

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