title: Hemodynamics associated with atrial fibrillation directly alters thrombotic potential of endothelial cells.
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.
authors.affiliation: HemoShear Therapeutics, LLC, Charlottesville, VA, United States.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Simmers
authors.affiliation: HemoShear Therapeutics, LLC, Charlottesville, VA, United States.
authors.forename: Banumathi K
authors.initials: BK
authors.lastname: Cole
authors.affiliation: Merck & Co, Merck Research Labs, Rahway, NJ, United States. Electronic address: Martin.Ogletree@Vanderbilt.edu.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Ogletree
authors.affiliation: Merck & Co, Merck Research Labs, Rahway, NJ, United States.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Merck & Co, Merck Research Labs, Rahway, NJ, United States.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Merck & Co, Merck Research Labs, Rahway, NJ, United States.
authors.forename: Ling-Jie
authors.initials: LJ
authors.lastname: Kong
authors.affiliation: University of North Carolina, Chapel Hill, NC, United States.
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
authors.affiliation: HemoShear Therapeutics, LLC, Charlottesville, VA, United States.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Blackman
authors.affiliation: HemoShear Therapeutics, LLC, Charlottesville, VA, United States. Electronic address: Wamhoff@HemoShear.com.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Wamhoff
mesh_terms: D020517:Atrial Appendage / Q000473:pathology*; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications* / Q000473:pathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology*; D005337:Fibrin / Q000032:analysis; D006439:Hemodynamics; D006801:Humans; D013927:Thrombosis / Q000097:blood* / Q000209:etiology* / Q000473:pathology
chemical_list: D005337:Fibrin
keywords: Atrial fibrillation; Left atrial appendage; Thrombosis