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The influence of Nrf2 on cardiac responses to environmental stressors
Howden, R., E. Gougian, M. Lawrence, S. Cividanes, W. Gladwell, L. Miller-DeGraff, P. Meyers, C. Rouse, R. Devlin, H. Cho, AND S. Kleeberger. The influence of Nrf2 on cardiac responses to environmental stressors. Oxidative Medicine and Cellular Longevity . Hindawi Publishing Corporation, New York, NY, 2013(901239):1-10, (2013).
Nrf2 protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role of Nrf2 on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption of Nrf2 would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures. Nrf2-/- and Nrf2+/+ mice were instrumented for continuous ECG recording to calculate HR and HRV [low frequency (LF), high frequency (HF) and total power (TP)]. Mice were then exposed to either hyperoxia for up to 72 hr or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P < 0.001) and HF HRV (P < 0.001) in Nrf2-/- mice compared to Nrf2+/+ mice. Nrf2-/- mice tolerated hyperoxia significantly less than Nrf2+/+ mice (~22 hours; P < 0.001). Reductions in HR, LF, HF and TP HRV were also significantly greater in Nrf2-/- compared to Nrf2+/+ mice (P 0.01). Results demonstrate that Nrf2 deletion increases susceptibility to changes in HR and HRV responses to environmental stressors, and suggest potential therapeutic strategies to prevent cardiovascular alterations.
This manuscript describes a gene and biologic pathway that makes individuals more responsive to air pollutants that cause oxidative stress.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION