The Effects of Exercise, Aspirin, and Celecoxib in an Atherogenic Environment

Introduction Optimal vascular function is a hallmark of cardiovascular health. Specifically, the balance of vasoconstricting and vasodilating substances is recognized as a marker of vascular health. One of the greatest challenges to vascular health and vasodilatory balance is tumor necrosis factor alpha (TNFα) mediated inflammation. Uncovering effective strategies that maintain a vascular environment that is more vasodilatory and anti-thrombotic in the face of an inflammatory challenge is favorable. Purpose: To test the ability of various anti-thrombotic and pro-vasodilatory treatments, as well as combinations thereof, to prevent unfavorable changes in markers of endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) when presented with an inflammatory challenge. Methods HUVECs were pre-treated with exercise-like levels of laminar shear stress (LSS), aspirin, celecoxib, and their combination prior to a TNFα challenge. Western blot analysis, as well as colorimetric assays were used to determine levels of eNOS and prostacyclin (6-keto PGF1α)/thromboxane (TXB2) metabolite ratio, respectively. Results Neither aspirin, nor celecoxib were effective in preventing TNFα-induced reduction in eNOS. Further, aspirin was unable to maintain baseline levels of prostacyclin/thromboxane ratio in the face of the inflammatory challenge. LSS, aspirin/LSS combination, and celecoxib/LSS combination were all able to prevent TNFα-induced alterations in eNOS levels and prostacyclin/thromboxane ratio. Conclusion Effective strategies to maintain a healthy endothelium and therefore resistance vessel health, need to include exercise-levels of shear stress to be effective. Author Correspondence: Heather Grimm, Ph.D., King's College, Sports Medicine Department, 133 North River St., Wilkes-Barre, PA 18711 The authors would like to thank the University of Illinois at Chicago and our Generosity by Indiegogo contributors for financial support of this study. The authors do not have any conflicts of interest that might bias the work. The results of the current study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation and do not constitute endorsement by the American College of Sports Medicine. Accepted for Publication: 16 April 2018 © 2018 American College of Sports Medicine

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