A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis.
Blood
; 138(13): 1182-1193, 2021 09 30.
Article
in En
| MEDLINE
| ID: mdl-33945603
ABSTRACT
Events mediated by the P-selectin/PSGL-1 pathway play a critical role in the initiation and propagation of venous thrombosis by facilitating the accumulation of leukocytes and platelets within the growing thrombus. Activated platelets and endothelium express P-selectin, which binds P-selectin glycoprotein ligand-1 (PSGL-1) that is expressed on the surface of all leukocytes. We developed a pegylated glycomimetic of the N terminus of PSGL-1, PEG40-GSnP-6 (P-G6), which proved to be a highly potent P-selectin inhibitor with a favorable pharmacokinetic profile for clinical translation. P-G6 inhibits human and mouse platelet-monocyte and platelet-neutrophil aggregation in vitro and blocks microcirculatory platelet-leukocyte interactions in vivo. Administration of P-G6 reduces thrombus formation in a nonocclusive model of deep vein thrombosis with a commensurate reduction in leukocyte accumulation, but without disruption of hemostasis. P-G6 potently inhibits the P-selectin/PSGL-1 pathway and represents a promising drug candidate for the prevention of venous thrombosis without increased bleeding risk.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombosis
/
Membrane Glycoproteins
/
P-Selectin
Limits:
Animals
/
Humans
Language:
En
Journal:
Blood
Year:
2021
Document type:
Article
Affiliation country: