Evidence for tissue factor expression in aortic valves in patients with aortic stenosis

INTRODUCTION: The role of blood coagulation in the pathogenesis of aortic stenosis (AS) is unknown. Recently, tissue factor (TF) expression in stenotic aortic valves has been reported in animal model. OBJECTIVES: The aim of the study was to investigate TF expression in valve leaflets obtained from AS patients and to determine its associations with circulating coagulation markers and echocardiographic variables. PATIENTS AND METHODS: We studied 20 patients (10 men, 10 women) with dominant AS (age 62.9 ±9.6, years, mean gradient 43.62 ±14.62 mmHg), and 20 well‑matched patients with dominant aortic insufficiency (AI) undergoing elective aortic valve replacement. Immunofluorescence was measured on decalcified leaflets using antibodies against human TF and macrophages. Prothrombin fragment 1+2 (F1+2) and circulating TF were determined in plasma prior to surgery. RESULTS: AS valves were characterized by an increased (all, p <0.001) percentage of TF‑positive (24.6%) and macrophage‑containing (27.3%) areas detected mainly on the aortic side of the leaflets, compared with AI valves (6.3% and 7.4%, respectively). Patients with AS had elevated F1+2 (262.1 ±27.8 pmol/l, p <0.001) and plasma TF (median 131.8, interquartile range [91.42–310.56] pg/ml, p = 0.018) compared with AI subjects (136.1 ±11.9 pmol/l, 65.38 [49.51–87.81] pg/ml, respectively). Percentage of TF‑positive areas correlated with plasma TF (r = 0.68, p <0.0001), but not with F1+2. Maximum transvalvular gradient >75 mmHg, but not the aortic valve area, showed associations with percentage of TF‑positive areas (r = 0.88, p = 0.0039). CONCLUSIONS: This study is the first full‑length report demonstrating the presence of TF associated with macrophage infiltration in human aortic valve leaflets in AS patients.