The contribution of the sinusoidal endothelial cell receptors CLEC4M, stabilin-2, and SCARA5 to VWF-FVIII clearance in thrombosis and hemostasis.
J Thromb Haemost
; 21(8): 2007-2019, 2023 08.
Article
en En
| MEDLINE
| ID: mdl-37085036
ABSTRACT
Quantitative abnormalities in factor VIII (FVIII) and its binding partner, von Willebrand factor (VWF), are associated with an increased risk of bleeding or thrombosis, and pathways that regulate the clearance of VWF-FVIII can strongly influence their plasma levels. In 2010, the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) on genome-wide association study meta-analysis identified variants in the genes for the sinusoidal endothelial receptors C-type lectin domain family 4 member M (CLEC4M), stabilin-2, and scavenger receptor class A member 5 (SCARA5) as being associated with plasma levels of VWF and/or FVIII in normal individuals. The ability of these receptors to bind, internalize, and clear the VWF-FVIII complex from the circulation has now been reported in a series of studies using in vitro and in vivo models. The receptor stabilin-2 has also been shown to modulate the immune response to infused VWF-FVIII concentrates in a murine model. In addition, the influence of genetic variants in CLEC4M, STAB2, and SCARA5 on type 1 von Willebrand disease/low VWF phenotype, FVIII pharmacokinetics, and the risk of venous thromboembolism has been described in a number of patient-based studies. Understanding the role of these receptors in the regulation of VWF-FVIII clearance has led to significant insights into the genomic architecture that modulates plasma VWF and FVIII levels, improving the understanding of pathways that regulate VWF-FVIII clearance and the mechanistic basis of quantitative VWF-FVIII pathologies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trombosis
/
Enfermedades de von Willebrand
/
Hemostáticos
Tipo de estudio:
Prognostic_studies
/
Systematic_reviews
Límite:
Animals
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Canadá