In:
Haematologica, Ferrata Storti Foundation (Haematologica), Vol. 107, No. 11 ( 2022-04-21), p. 2650-2660
Abstract:
Sickle cell disease (SCD) is an inherited red blood cell disorder that occurs worldwide. Acute vaso-occlusive crisis is the main cause of hospitalization in patients with SCD. There is growing evidence that inflammatory vasculopathy plays a key role in both acute and chronic SCD-related clinical manifestations. In a humanized mouse model of SCD, we found an increase of von Willebrand factor activity and a reduction in the ratio of a disintegrin and metalloproteinase with thrombospondin type 1 motif, number 13 (ADAMTS13) to von Willebrand factor activity similar to that observed in the human counterpart. Recombinant ADAMTS13 was administered to humanized SCD mice before they were subjected to hypoxia/reoxygenation (H/R) stress as a model of vaso-occlusive crisis. In SCD mice, recombinant ADAMTS13 reduced H/R-induced hemolysis and systemic and local inflammation in lungs and kidneys. It also diminished H/R-induced worsening of inflammatory vasculopathy, reducing local nitric oxidase synthase expression. Collectively, our data provide for the firsttime evidence that pharmacological treatment with recombinant ADAMTS13 (TAK-755) diminished H/R-induced sickle cell-related organ damage. Thus, recombinant ADAMTS13 might be considered as a potential effective disease-modifying treatment option for sickle cell-related acute events.
Type of Medium:
Online Resource
ISSN:
1592-8721
,
0390-6078
DOI:
10.3324/haematol.2021.280233
Language:
Unknown
Publisher:
Ferrata Storti Foundation (Haematologica)
Publication Date:
2022
detail.hit.zdb_id:
2186022-1
detail.hit.zdb_id:
2030158-3
detail.hit.zdb_id:
2805244-4