title: Circulating Microparticles Alter Formation, Structure, and Properties of Fibrin Clots.
abstract: Despite the importance of circulating microparticles in haemostasis and thrombosis, there is limited evidence for potential causative effects of naturally produced cell-derived microparticles on fibrin clot formation and its properties. We studied the significance of blood microparticles for fibrin formation, structure, and susceptibility to fibrinolysis by removing them from platelet-free plasma using filtration. Clots made in platelet-free and microparticle-depleted plasma samples from the same healthy donors were analyzed in parallel. Microparticles accelerate fibrin polymerisation and support formation of more compact clots that resist internal and external fibrinolysis. These variations correlate with faster thrombin generation, suggesting thrombin-mediated kinetic effects of microparticles on fibrin formation, structure, and properties. In addition, clots formed in the presence of microparticles, unlike clots from the microparticle-depleted plasma, contain 0.1-0.5-μm size granular and CD61-positive material on fibres, suggesting that platelet-derived microparticles attach to fibrin. Therefore, the blood of healthy individuals contains functional microparticles at the levels that have a procoagulant potential. They affect the structure and stability of fibrin clots indirectly through acceleration of thrombin generation and through direct physical incorporation into the fibrin network. Both mechanisms underlie a potential role of microparticles in haemostasis and thrombosis as modulators of fibrin formation, structure, and resistance to fibrinolysis.
authors.affiliation: Department of General Pathology, Kazan State Medical University, Kazan 420012, Russian Federation.
authors.forename: Laily D
authors.initials: LD
authors.lastname: Zubairova
authors.affiliation: Department of General Pathology, Kazan State Medical University, Kazan 420012, Russian Federation.
authors.forename: Roza M
authors.initials: RM
authors.lastname: Nabiullina
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Chandrasekaran
authors.initials: C
authors.lastname: Nagaswami
authors.affiliation: Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan 420111, Russian Federation.
authors.forename: Yuriy F
authors.initials: YF
authors.lastname: Zuev
authors.affiliation: Department of General Pathology, Kazan State Medical University, Kazan 420012, Russian Federation.
authors.forename: Ilshat G
authors.initials: IG
authors.lastname: Mustafin
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.|Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420012, Russian Federation.
authors.forename: Rustem I
authors.initials: RI
authors.lastname: Litvinov
authors.affiliation: Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Weisel
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism*; D005342:Fibrinolysis; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood* / Q000378:metabolism / Q000473:pathology
chemical_list: D005337:Fibrin; D013917:Thrombin