TY - JOUR
T1 - Extracellular vesicles from amniotic fluid, milk, saliva, and urine expose complexes of tissue factor and activated factor VII
AU - Hu, Yong
AU - Repa, Andreas
AU - Lisman, Ton
AU - Yerlikaya-Schatten, Guelen
AU - Hau, Chi
AU - Pabinger, Ingrid
AU - Ay, Cihan
AU - Nieuwland, Rienk
AU - Thaler, Johannes
N1 - Funding Information: Y.H. was supported by a scholarship from the China Scholarship Council (CSC). J.T. was supported by an unrestricted travel grant from the International Society on Thrombosis and Haemostasis. The authors thank Jenny M.M.H. van den Goor (Amsterdam University Medical Center, University of Amsterdam, Amsterdam) for pericardial wound blood collection at the Department of Cardio‐thoracic Surgery of the Amsterdam University Medical Center, University of Amsterdam, and Jelle Adelmeijer from the University Medical Center Groningen for performing fibrinolysis experiments. Publisher Copyright: © 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.
PY - 2022/10
Y1 - 2022/10
N2 - Background: Tissue factor (TF) is expressed in the adventitia of the vessel wall and on extracellular vesicles (EVs) in body fluids. TF and activated coagulation factor (F) VII(a) together form the so-called extrinsic tenase complex, which initiates coagulation. Aim: We investigated whether EVs in amniotic fluid, milk, saliva, and urine expose functional extrinsic tenase complexes that can trigger coagulation. Methods: Milk, saliva, and urine were collected from healthy breastfeeding women (n = 6), and amniotic fluid was collected from healthy women undergoing routine amniocentesis (n = 7). EVs were isolated from body fluids by size exclusion chromatography (SEC) and clotting experiments were performed in the presence and absence of antibodies against TF and FVIIa in normal plasma and in FVII-deficient plasma. The ability of body fluids to generate FXa also was determined. Results: Amniotic fluid, milk, saliva, and urine triggered clotting of normal plasma and of FVII-deficient plasma, which was almost completely inhibited by an anti-FVII antibody and to a lesser extent by an anti-TF antibody. Fractionation of body fluids by SEC showed that only the fractions containing EVs triggered clotting in normal plasma and FVII-deficient plasma and generated FXa, which again was almost completely inhibited by an anti-FVII antibody and partially by an anti-TF antibody. Conclusion: Here we show that EVs from amniotic fluid, milk, saliva, and urine expose complexes of TF and FVIIa (i.e., extrinsic tenase complexes) that directly activate FX. Based on our present findings we propose that these EVs from normal body fluids provide hemostatic protection.
AB - Background: Tissue factor (TF) is expressed in the adventitia of the vessel wall and on extracellular vesicles (EVs) in body fluids. TF and activated coagulation factor (F) VII(a) together form the so-called extrinsic tenase complex, which initiates coagulation. Aim: We investigated whether EVs in amniotic fluid, milk, saliva, and urine expose functional extrinsic tenase complexes that can trigger coagulation. Methods: Milk, saliva, and urine were collected from healthy breastfeeding women (n = 6), and amniotic fluid was collected from healthy women undergoing routine amniocentesis (n = 7). EVs were isolated from body fluids by size exclusion chromatography (SEC) and clotting experiments were performed in the presence and absence of antibodies against TF and FVIIa in normal plasma and in FVII-deficient plasma. The ability of body fluids to generate FXa also was determined. Results: Amniotic fluid, milk, saliva, and urine triggered clotting of normal plasma and of FVII-deficient plasma, which was almost completely inhibited by an anti-FVII antibody and to a lesser extent by an anti-TF antibody. Fractionation of body fluids by SEC showed that only the fractions containing EVs triggered clotting in normal plasma and FVII-deficient plasma and generated FXa, which again was almost completely inhibited by an anti-FVII antibody and partially by an anti-TF antibody. Conclusion: Here we show that EVs from amniotic fluid, milk, saliva, and urine expose complexes of TF and FVIIa (i.e., extrinsic tenase complexes) that directly activate FX. Based on our present findings we propose that these EVs from normal body fluids provide hemostatic protection.
KW - body fluids
KW - coagulation factor VII
KW - extracellular vesicles
KW - extrinsic tenase complexes
KW - tissue factor
UR - http://www.scopus.com/inward/record.url?scp=85135129412&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/jth.15801
DO - https://doi.org/10.1111/jth.15801
M3 - Article
C2 - 35748324
SN - 1538-7933
VL - 20
SP - 2306
EP - 2312
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 10
ER -