The aptamer BT200 effectively inhibits von Willebrand factor (VWF) dependent platelet function after stimulated VWF release by desmopressin or endotoxin.
Adenosine Diphosphate
/ metabolism
Adult
Aptamers, Nucleotide
/ pharmacology
Blood Platelets
/ drug effects
Cells, Cultured
Collagen
/ metabolism
Deamino Arginine Vasopressin
/ pharmacology
Female
Humans
Lipopolysaccharides
/ pharmacology
Male
Middle Aged
Platelet Aggregation
von Willebrand Factor
/ antagonists & inhibitors
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
07 07 2020
07 07 2020
Historique:
received:
23
03
2020
accepted:
05
06
2020
entrez:
9
7
2020
pubmed:
9
7
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Von Willebrand factor (VWF) plays a major role in arterial thrombosis. Antiplatelet drugs induce only a moderate relative risk reduction after atherothrombosis, and their inhibitory effects are compromised under high shear rates when VWF levels are increased. Therefore, we investigated the ex vivo effects of a third-generation anti-VWF aptamer (BT200) before/after stimulated VWF release. We studied the concentration-effect curves BT200 had on VWF activity, platelet plug formation under high shear rates (PFA), and ristocetin-induced platelet aggregation (Multiplate) before and after desmopressin or endotoxin infusions in healthy volunteers. VWF levels increased > 2.5-fold after desmopressin or endotoxin infusion (p < 0.001) and both agents elevated circulating VWF activity. At baseline, 0.51 µg/ml BT200 reduced VWF activity to 20% of normal, but 2.5-fold higher BT200 levels were required after desmopressin administration (p < 0.001). Similarly, twofold higher BT200 concentrations were needed after endotoxin infusion compared to baseline (p < 0.011). BT200 levels of 0.49 µg/ml prolonged collagen-ADP closure times to > 300 s at baseline, whereas 1.35 µg/ml BT200 were needed 2 h after desmopressin infusion. Similarly, twofold higher BT200 concentrations were necessary to inhibit ristocetin induced aggregation after desmopressin infusion compared to baseline (p < 0.001). Both stimuli elevated plasma VWF levels in a manner representative of thrombotic or pro-inflammatory conditions such as arterial thrombosis. Even under these conditions, BT200 potently inhibited VWF activity and VWF-dependent platelet function, but higher BT200 concentrations were required for comparable effects relative to the unstimulated state.
Identifiants
pubmed: 32636459
doi: 10.1038/s41598-020-68125-9
pii: 10.1038/s41598-020-68125-9
pmc: PMC7341806
doi:
Substances chimiques
Aptamers, Nucleotide
0
Lipopolysaccharides
0
von Willebrand Factor
0
Adenosine Diphosphate
61D2G4IYVH
Collagen
9007-34-5
Deamino Arginine Vasopressin
ENR1LLB0FP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11180Références
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