title: Limited ability to activate protein C confers left atrial endocardium a thrombogenic phenotype: a role in cardioembolic stroke?
abstract: OBJECTIVE
  Atrial fibrillation is the most important risk factor for cardioembolic stroke. Thrombi form in the left atrial appendage rather than in the right. The causes of this different thrombogenicity are not well-understood. The goal herein was to compare the activation of the anticoagulant protein C and the thrombomodulin and endothelial protein C receptor/activated protein C receptor expression on the endocardium between right and left atria.
  
  
  METHODS
  We harvested the atria of 6 monkeys (Macaca fascicularis) and quantified their ability to activate protein C ex vivo and we measured the thrombomodulin and endothelial protein C receptor expression by immunofluorescence.
  
  
  RESULTS
  We found the ability to activate protein C decreased by half (P=0.028) and there was lower expression of thrombomodulin in the left atrial endocardium than the right (52.5±19.9 and 72.1±18.8 arbitrary intensity units, mean±standard deviation; P=0.028). No differences were detected in endothelial protein C receptor expression.
  
  
  CONCLUSIONS
  Impaired protein C activation on the left atrial endocardium attributable to low thrombomodulin expression may explain its higher thrombogenicity and play a role in cardioembolic stroke.
authors.affiliation: Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Avenida Pío XII, 55, 31008 Pamplona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cerveró
authors.forename: Ramón
authors.initials: R
authors.lastname: Montes
authors.forename: Francisco
authors.initials: F
authors.lastname: España
authors.forename: Charles T
authors.initials: CT
authors.lastname: Esmon
authors.forename: José
authors.initials: J
authors.lastname: Hermida
mesh_terms: D000818:Animals; D020517:Atrial Appendage / Q000378:metabolism* / Q000473:pathology; D001281:Atrial Fibrillation / Q000150:complications / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000096:biosynthesis*; D004699:Endocardium / Q000378:metabolism* / Q000473:pathology; D004727:Endothelium / Q000378:metabolism; D005786:Gene Expression Regulation; D008252:Macaca fascicularis; D010641:Phenotype; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D020521:Stroke / Q000209:etiology / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D001779:Blood Coagulation Factors; D011486:Protein C; D011956:Receptors, Cell Surface; D018180:Thrombomodulin; C091963:activated protein C receptor