P14: Vibration-Mediated Endothelial Cell-Platelet Interaction: A Thrombotic Risk Factor in Obstructive Sleep Apnea and Beyond

Abstract

Background: Obstructive sleep apnea (OSA) is an independent risk factor for thrombotic stroke. OSA stroke is felt to be driven by hypoxia and post apneacatecholamine surge, leading to platelet activation and thrombosis. OSA is also associated with significant snoring and related neck vibration. In our work related to thrombogenicity of mechanical circulatory support (MCS) devices we demonstrated that device vibration and related shear are biomechanical activators of platelets. Recently we showed that snore-associated vibration is platelet activating. As OSA snore, vibration is imparted to major neck blood vessels, i.e. carotid and jugular, and activated platelets interact with vessel endothelial cells, the effect of vibration on endothelial thrombogenicity warrants further definition. Methods: OSA snore recordings were obtained from the human sleep lab. A speaker-platform device, validated to generate snore neck vibrations, was fabricated (snore emulator). Human umbilical vein endothelial cells (HUVECs) grown on petri dishes, placed on the emulator and exposed to snore vibrations for 4,8,12, 24,or 36 hours at 37oC., non-vibration cultures serving as controls. HUVEC viability (LDH assay) and platelet adhesion (inactivated platelets bound, measured via scanning EM) were serially assessed. Results: HUVEC exposed to snore vibration remained viable, though with a progressive decline in viability vs control, i.e. a 28.9% and 46.5% reduction at 24h and 36h, respectively (p<0.05). Interestingly, vibration led to a disproportionally greater increase in thrombogenicity, with net platelet adhesion increasing by 64% and 86% at 24h and 36h respectively (p<0.05) Conclusion: Vibration, as a general biomechanical stimulus, previously demonstrated to increase platelet activation, also leads to endothelial dysfunction, including loss of viability, with an even greater increase in endothelial thrombogenicity. Further definition of vibration-mediated endothelial dysfunction has implication for developing translational therapeutics for OSA, as well as providing insight for endothelial-contacting therapeutic device design.