Format

Send to

Choose Destination
Blood. 2016 Mar 17;127(11):1493-501. doi: 10.1182/blood-2015-02-629667. Epub 2016 Jan 11.

Lysyl oxidase is associated with increased thrombosis and platelet reactivity.

Author information

1
Department of Medicine and Whitaker Cardiovascular Institute and.
2
Department of Biochemistry, Boston University School of Medicine, Boston, MA;
3
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA;
4
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.
5
Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA.
6
Department of Medicine and Whitaker Cardiovascular Institute and Department of Biochemistry, Boston University School of Medicine, Boston, MA;

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.

PMID:
26755713
PMCID:
PMC4797025
DOI:
10.1182/blood-2015-02-629667
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center