title: Lysyl oxidase is associated with increased thrombosis and platelet reactivity.
abstract: Lysyl oxidase (LOX) is overexpressed in various pathologies associated with thrombosis, such as arterial stenosis and myeloproliferative neoplasms (MPNs). LOX is elevated in the megakaryocytic lineage of mouse models of MPNs and in patients with MPNs. To gain insight into the role of LOX in thrombosis and platelet function without compounding the influences of other pathologies, transgenic mice expressing LOX in wild-type megakaryocytes and platelets (Pf4-Lox(tg/tg)) were generated. Pf4-Lox(tg/tg) mice had a normal number of platelets; however, time to vessel occlusion after endothelial injury was significantly shorter in Pf4-Lox(tg/tg) mice, indicating a higher propensity for thrombus formation in vivo. Exploring underlying mechanisms, we found that Pf4-Lox(tg/tg) platelets adhere better to collagen and have greater aggregation response to lower doses of collagen compared with controls. Platelet activation in response to the ligand for collagen receptor glycoprotein VI (cross-linked collagen-related peptide) was unaffected. However, the higher affinity of Pf4-Lox(tg/tg) platelets to the collagen sequence GFOGER implies that the collagen receptor integrin α2β1 is affected by LOX. Taken together, our findings demonstrate that LOX enhances platelet activation and thrombosis.
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and.
authors.forename: Shinobu
authors.identifier: http://orcid.org/0000-0002-3914-5376
authors.initials: S
authors.lastname: Matsuura
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and.
authors.forename: Rongjuan
authors.initials: R
authors.lastname: Mi
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and.
authors.forename: Milka
authors.initials: M
authors.lastname: Koupenova
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA;
authors.forename: Alexia
authors.initials: A
authors.lastname: Eliades
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and.
authors.forename: Shenia
authors.identifier: http://orcid.org/0000-0003-4533-8518
authors.initials: S
authors.lastname: Patterson
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA;
authors.forename: Paul
authors.initials: P
authors.lastname: Toselli
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0002-7969-7001
authors.initials: J
authors.lastname: Thon
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA; and.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
authors.affiliation: Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA.
authors.forename: Philip C
authors.identifier: http://orcid.org/0000-0001-5064-614X
authors.initials: PC
authors.lastname: Trackman
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papadantonakis
authors.affiliation: Department of Medicine and Whitaker Cardiovascular Institute and Department of Biochemistry, Boston University School of Medicine, Boston, MA;
authors.forename: Katya
authors.identifier: http://orcid.org/0000-0002-9918-3024
authors.initials: K
authors.lastname: Ravid
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D020212:Carotid Artery Injuries / Q000150:complications; D002341:Carotid Artery Thrombosis / Q000209:etiology; D003094:Collagen / Q000494:pharmacology*; D038982:Integrin alpha2beta1 / Q000502:physiology; D008533:Megakaryocytes / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000494:pharmacology; D015539:Platelet Activation / Q000502:physiology*; D010973:Platelet Adhesiveness / Q000235:genetics / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010978:Platelet Factor 4 / Q000235:genetics; D011401:Promoter Regions, Genetic; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000502:physiology*; D051381:Rats; D019851:Thrombophilia / Q000201:enzymology* / Q000235:genetics
chemical_list: D038982:Integrin alpha2beta1; D010446:Peptide Fragments; D010978:Platelet Factor 4; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase