title: von Willebrand factor multimer composition is modified following oral methionine load in women with thrombosis, but not in healthy women.
abstract: Hyperhomocysteinemia is associated with an increased risk of venous and arterial thrombosis, probably by inducing endothelial damage. Von Willebrand factor (VWF) is an endothelial marker protein. It is a plasma multimeric molecule that plays a thrombophilic role. Our purpose was to investigate VWF changes in patients with thrombosis following oral methionine load. We evaluated homocysteine levels and VWF parameters (plasma levels, activity, proteolysis fragments, and multimer composition) before and after methionine load in 42 women with venous or arterial thrombosis and in 36 healthy women. Methionine load induced mild hyperhomocysteinemia in 10 patients and two controls. No changes in VWF levels and activity were observed, but an increased amount of VWF proteolysis fragments was found post-load in patients and controls. VWF multimer composition was unaffected in controls, while a decrease of the largest VWF multimers was found in women with thrombosis. Homocysteine levels inversely correlated with the amount of the largest multimers in hyperhomocysteinemic patients. Large VWF molecules were probably released from endothelial cells following load, and rapidly cleaved by the specific VWF-cleaving protease. VWF proteolysis was enhanced in mild hyperhomocysteinemic patients, thus leading to downregulation of VWF size to smaller multimers.
authors.affiliation: Thrombosis and Hemostasis Unit, Department of Hematology and Oncology, IRCCS G. Gaslini, Largo G. Gaslini 5, I-16147 Genoa, Italy. paoloperutelli@ospedale-gaslini.ge.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Perutelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Amato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.forename: Federico
authors.initials: F
authors.lastname: Bottini
authors.forename: Maria G
authors.initials: MG
authors.lastname: Calevo
authors.forename: Roberto
authors.initials: R
authors.lastname: Cerone
authors.forename: Angelo C
authors.initials: AC
authors.lastname: Molinari
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019281:Dimerization; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000139:chemically induced; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000378:metabolism; D013927:Thrombosis / Q000097:blood*; D014841:von Willebrand Factor / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D014841:von Willebrand Factor; D006710:Homocysteine; D008715:Methionine; D010447:Peptide Hydrolases