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.