HemoShear Therapeutics, LLC, Charlottesville, VA, United States.
Merck & Co, Merck Research Labs, Rahway, NJ, United States.
Thromb Res. 2016 Jul;143:34-9. doi: 10.1016/j.thromres.2016.04.022. Epub 2016 Apr 27.
An experimental in vitro model of the hemodynamics that occur in atrial fibrillation (AFib) in the left atrial appendage (LAA) was developed to study changes in human endothelial cell thrombotic potential. We applied human-derived sinus rhythm and AFib hemodynamic shear stress patterns to primary human endothelial cells (ECs) in culture. We found that ECs exposed to AFib hemodynamics have increased thrombotic potential as measured by increased expression of pro-thrombotic gene markers and fibrin deposition on the endothelium. Treatment with the factor Xa inhibitor, apixaban, attenuated fibrin deposition thickness while increasing fibrin density at the endothelial cell surface. This study suggests that altered hemodynamics associated with AFib play a key role in driving the thrombotic potential of the LAA endothelium.
我们开发了一种左心耳（LAA）中发生房颤（AFib）时血液动力学的体外实验模型，以研究人类内皮细胞血栓形成潜力的变化。我们将源自人类的窦性节律和 AFib 血液动力学切应力模式应用于培养中的原代人内皮细胞（ECs）。我们发现，暴露于 AFib 血流的 ECs 表现出增加的血栓形成潜力，这可通过增加促血栓形成基因标记物的表达和内皮细胞上的纤维蛋白沉积来衡量。用因子 Xa 抑制剂阿哌沙班治疗可减轻纤维蛋白沉积厚度，同时增加内皮细胞表面的纤维蛋白密度。这项研究表明，与 AFib 相关的血液动力学改变在驱动 LAA 内皮细胞的血栓形成潜力方面起着关键作用。
