title: SV-IV Peptide1-16 reduces coagulant power in normal Factor V and Factor V Leiden.
abstract: Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance. Factor V Leiden (FVL) disorder may lead to thrombophilia. Whether a reduction in the activation of Factor V or Factor V Leiden may correct the disposition to thrombophilia is unknown. Therefore we tested SV-IV Peptide 1-16 (i.e. a peptide derived by seminal protein vescicle number IV, SV-IV) to assess its capacity to inhibit the procoagulant activity of normal clotting factor V or Factor V Leiden (FVL). We found that SV-IV protein has potent anti-inflammatory and immunomodulatory properties and also exerts procoagulant activity. In the present work we show that the SV-IV Peptide 1-16, incubated with plasma containing normal Factor V or FVL plasma for 5 minutes reduces the procoagulant capacity of both substances. This is an anticoagulant effect whereas SV-IV protein is a procoagulant. This activity is effective both in terms of the coagulation tests, where coagulation times are increased, and in terms of biochemical tests conducted with purified molecules, where Factor X activation is reduced. Peptide 1-16 was, in the pure molecule system, first incubated for 5 minutes with purified Factor V then it was added to the mix of phosphatidylserine, Ca2+, Factor X and its chromogenic molecule Chromozym X. We observed a more than 50% reduction in lysis of chromogenic molecule Chromozym X by Factor Xa, compared to the sample without Peptide 1-16. Such reduction in Chromozym X lysis, is explained with the reduced activation of Factor X by partial inactivation of Factor V by Peptide 1-16. Thus our study demonstrates that Peptide 1-16 reduces the coagulation capacity of Factor V and Factor V Leiden in vitro, and, in turn, causes factor X reduced activation.
authors.affiliation: Department of Internal Medicine, Buon Consiglio Fatebenefratelli Hospital of Naples, Italy. biagio.dimicco@fastwebnet.it
authors.forename: Biagio
authors.initials: B
authors.lastname: Di Micco
authors.forename: Marilena
authors.initials: M
authors.lastname: Lepretti
authors.forename: Lidia
authors.initials: L
authors.lastname: Rota
authors.forename: Ilaria
authors.initials: I
authors.lastname: Quaglia
authors.forename: Paola
authors.initials: P
authors.lastname: Ferrazzi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Di Micco
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Di Micco
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood; D000595:Amino Acid Sequence; D001777:Blood Coagulation / Q000187:drug effects*; D005165:Factor V / Q000032:analysis; D005170:Factor X; D015951:Factor Xa; D006801:Humans; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000494:pharmacology*; D029607:Seminal Vesicle Secretory Proteins / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; D029607:Seminal Vesicle Secretory Proteins; C095381:factor V Leiden; D005165:Factor V; D005170:Factor X; D015951:Factor Xa