Exercise-levels Of Laminar Shear Stress In Combination Of Aspirin And Celecoxib Normalize An Atherognic Environment

Optimal vascular function is a hallmark of cardiovascular health. Specifically, the balance of vasoconstricting and vasodilating substances in the vascular bed is recognized as a surrogate measure of the health of resistance vessels. Endothelial Nitrix Oxide Synthase (eNOS) is considered to be one of the best indicators of vasokine balance in these vessels, with high levels of expression being considered to be favorable. Further, the balance of the vasodilating/anti-thrombotic substance prostacyclin and vasoconstricing/ pro-thrombotic substance thromboxane in the endothelial cell layer is a further indicator of the overall health of the cardiovascular system. One of the greatest challenges to vascular health and vasodilatory balance is 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 disruptions of vascular health of endothelial cells when faced with an inflammatory challenge in the form of TNFα. METHODS: Human Umbilical Vein Endothelial Cells HUVECs were pre-treated exercise-like levels of laminar shear stress (LSS), aspirin, celecoxib, and their combination prior to a TNFα challenge. Western blot analysis, as well as calorimetric assays were used to determine levels of eNOS and prostacyclin (6-keto PGF1α)/thromboxane (TXB2) metabolite ratio, respectively. RESULTS: Neither aspirin, nor celecoxib was 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 reductions 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.