Abstract 17483: Tert-butylhydroquinone Induces Gene Expression of Anti-oxidant Enzymes in Human Coronary Artery Endothelial Cells After Cyclosporine Treatment
Introduction: Cyclosporine (CsA) is an important immunosuppressant; however it may lead to oxidative stress in coronary vasculature and subsequently cardiac allograft vasculopathy (CAV). We previously demonstrated that CsA impairs kinematics of the master antioxidant gene regulator - nuclear factor erythroid 2–related factor 2 (Nrf2) in Human Coronary Artery Endothelial Cells (HCAECs).
Hypothesis: We assessed the hypothesis that tert-hydroquinone (tBHQ), an Nrf2 agonist, rescues CsA-mediated downregulation of antioxidant enzymes via increase in gene expression of Nrf2.
Methods: HCAECs (n=6) were treated with 50μg/ml CsA ± 20μM tBHQ or tBHQ alone for 2 hours. Control (CON) groups received 0.1% DMSO. Quantitative-real time polymerase chain reaction was performed to assess gene expression of NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), superoxide dismutase 1 (SOD1), and -2 (SOD2) at 2 hours. We also assessed Nrf2 gene expression at 2 hours.
Results: Compared to control, CsA decreased the expression of NQO1, SOD1, and SOD2, but not HO-1. Exposure to tBHQ alone resulted in increased expression of NQO1, SOD2, and Nrf2, but not HO-1, and SOD1 compared to control. When cells were exposed to both tBHQ and CsA, we determined that expressions of NQO1, HO-1, SOD2 and Nrf2 were synergistically upregulated. Concomitant exposure to tBHQ partially restored the downregulated expression of SOD1 compared to CsA alone, but did not achieve control levels.
Conclusion: Oxidative stress is increasingly known as a key component in pathogenesis of post-heart transplant coronary vasculopathy which is associated with morbidity and mortality. In conclusion, heart transplant patients who receive CsA therapy, may benefit from exposure to tBHQ since tBHQ-CsA co-therapy may mitigate coronary artery oxidative stress.
Author Disclosures: A. Ghashghai: None. D. Banner: None. R. Ribeiro: None. M. Degan: None. M. Badiwala: None. V. Rao: None.
- © 2016 by American Heart Association, Inc.