Hemodynamics associated with atrial fibrillation directly alters thrombotic potential of endothelial cells. Issue 143 (July 2016)

• Record Type: Journal Article
• Authors: Simmers, Michael B.; Cole, Banumathi K.; Ogletree, Martin L.; Chen, Zhu; Xu, Yiming; Kong, Ling-jie; Mackman, Nigel; Blackman, Brett R.; Wamhoff, Brian R.
• Is Part Of: Thrombosis research. Issue 143(2016)
• Page Start: 34
• Page End: 39
• Publication Date: 2016-07
• Subjects: (AFib) atrial fibrillation -- (LAA) left atrial appendage -- (ECs) endothelial cells -- (F3) tissue factor -- (vWF) von Willebrand Factor -- (ANGPT2) angiopoietin 2 -- (KFL2) kruppel-like factor-2 -- (eNOS) endothelial nitric oxide synthase -- (ECM) extracellular matrix -- (MMP14) matrix metalloproteinase-14 -- (TIMP2) tissue inhibitor of metalloproteinase-2 -- (TFPI) tissue factor pathway inhibitor; Atrial fibrillation -- Left atrial appendage -- Thrombosis; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.04.022
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: 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. Highlights: LAA atrial fibrillation (AFib) hemodynamics were applied to endothelial cells. AFib-exposed endothelial cells exhibited increased fibrin deposition. Markers of thrombosis are altered in AFib-exposed endothelial cells. Fibrin deposition thickness is reduced by apixaban in our experimental model.