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From the ECM to Thrombosis: a New Role for the Matrix Enzyme Lysyl Oxidase
Author(s) -
Matsuura Shinobu,
Mi Rongjuan,
Eliades Alexia,
Toselli Paul,
Thon Jonathan,
Italiano Joseph,
Trackman Philip,
Papadantonakis Nikolaos,
Ravid Katya
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.719.11
Subject(s) - lysyl oxidase , elastin , platelet , chemistry , thrombus , platelet activation , collagen receptor , platelet factor 4 , biochemistry , cancer research , medicine , integrin , immunology , pathology , extracellular matrix , receptor
Lysyl oxidase (LOX) catalyzes the oxidation of lysines to aldehydes, providing stability in connective tissues through spontaneous cross‐linking of collagen and elastin. LOX expression is elevated in sera of patients with myeloproliferative neoplasms (MPN), a group of disorders that have in common the proliferation of megakaryocytes and myelofibrosis in bone marrow. Thrombosis is a leading cause of morbidity and mortality in MPN, yet there is still controversy over contributors to the thrombotic events in MPN. Objective to test whether Lysyl Oxidase (LOX) is involved in the pathogenesis of thrombosis. Methods A transgenic mouse model expressing LOX in platelets ( Pf4‐Lox tg/tg ) was used to analyze platelet activation and thrombus formation. Results Vessel occlusion after endothelial injury was significantly shorter in Pf4‐Lox tg/tg mice, indicating a higher propensity for thrombus formation in vivo . While exploring mechanisms involved, we found that Pf4‐Lox tg/tg platelets adhere better to collagen. The higher affinity of Pf4‐Lox tg/tg platelets to monomeric compared to fibrillar collagen, as well as affinity to the GFOGER peptide implies integrin α 2 β 1 as the collagen receptor targeted by LOX. Taken together, our study identified LOX as a new regulator of collagen receptor and thus platelet activation and thrombosis.