Abstract 14471: Benzene Exposure Is Associated With Increased CVD Risk, Hyperlipidemia, and Decreased Circulating Angiogenic Cells in Humans and Mice
Introduction: Benzene is present in tobacco smoke, gasoline exhaust and industrial emissions, and while benzene exposure is known to disrupt hematopoiesis, the cardiovascular effects of exposure are unknown.
Hypothesis: Benzene exposure is associated with increased cardiovascular injury and increased cardiovascular disease (CVD) risk in human and murine exposure models.
Methods: Benzene exposure was assessed by measuring urinary levels of the benzene metabolite - trans,trans-muconic acid (t,t-MA) by UPLC-MS in 210 participants of the Louisville Healthy Heart Study with moderate to high CVD risk. Generalized linear models were used to assess the association between benzene exposure and CVD injury and risk after adjusting for confounders. Mice were exposed directly to volatile benzene (50ppm x 6h/d x 6wk) and indices of cardiovascular injury were measured.
Results: In our human cohort, t,t-MA levels were inversely associated with circulating levels of angiogenic cells: CD31+/34+/45+, CD31+/34+/45+/AC133- and CD34+/45+/AC133+. After adjusting for confounding, there was a 9% decrease in circulating levels of both early (CD34+/45+/AC133+) and late (CD31+/34+/45+/AC133-) cells for every 0.1 mg t,t-MA/g creatinine increase in the urine. Although t,t-MA was not associated with plasma markers of inflammation (C-reactive protein and fibrinogen) or thrombosis (platelet-monocyte aggregates), t,t-MA levels were higher in smokers and in individuals with hyperlipidemia (p<0.02). In smokers, t,t-MA levels were positively associated with urinary metabolites of nicotine (cotinine) and acrolein (3-hydroxypropylmercapturic acid). A positive association independent of smoking was found between urinary t,t-MA and CVD risk as measured by Framingham Risk Score. Benzene exposed mice demonstrated a 46% reduction (p=0.002) in circulating angiogenic cells (Flk-1+/Sca-1+), induced cytopenias in neutrophils, lymphocytes, monocytes and platelets, and increased plasma LDL:HDL ratio (23%, p=0.004) compared to mice exposed to filtered air.
Conclusions: Benzene exposure may increase CVD risk in both smokers and non-smokers by inducing deficits in vascular repair and dyslipidemia.
Author Disclosures: W. Abplanalp: None. N. DeJarnett: None. D. Riggs: None. X. Li: None. J. McCracken: None. R. Yeager: None. A. Defilippis: None. Z. Xie: None. D. Tollerud: None. D. Conklin: None. S. Rai: None. S. Srivastava: None. A. Bhatnagar: None. T. O’Toole: None.
- © 2016 by American Heart Association, Inc.