A mimetic of the RGDF-peptide [arginine-glycine-aspartic acid-phenylalanine] blocks aggregation and flow-induced platelet deposition on severely injured stenotic arterial wall. Effects on different animal models and in humans
1996
Abstract 8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the tetrapeptide arginine-glycine-aspartic acid-phelylalanine, inhibits fibrinogen and vitronectin binding to GP IIb IIIa . SC-49992 effects on impedance and optical aggregation were compared in different species (human, porcine and dog). SC-49992 induced significant inhibition both in whole blood and PRP aggregation, in all species; however, porcine platelets had a SC-49992 IC 50 = 2.5mM while human and dog platelets had a significant lower IC 5) (1μM and 1.5μM, respectively). Inhibition of flow-mediated platelet deposition on severely injured vessels was studied in porcine blood at high and low shear rates for 5 minutes. Additionally, studies were performed in vessels with 80% stenosis. SC-49992 reduced platelet deposition both at high and low shear rate in parallel streamlined flow and in stenotic conditions. The lower affinity of porcine platelets for SC-49992 seems to be due to a species difference at the GPIIb IIIa receptor RGD-sequence level.
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