1. The in vitro effects of a novel vascular protectant, AGI-1067, on platelet aggregation and major receptor expression in subjects with multiple risk factors for vascular disease.
- Author
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Serebruany V, Malinin A, and Scott R
- Subjects
- Adult, Antigens, CD biosynthesis, Antigens, CD drug effects, Baltimore, Biomarkers blood, Blood Platelets drug effects, Blood Platelets metabolism, Cell Adhesion Molecules biosynthesis, Cell Adhesion Molecules drug effects, Female, Flow Cytometry, Humans, Linear Models, Male, Middle Aged, Platelet Membrane Glycoproteins biosynthesis, Platelet Membrane Glycoproteins drug effects, Probucol pharmacology, Receptors, Cell Surface classification, Risk Factors, Vascular Diseases epidemiology, Antioxidants pharmacology, Platelet Aggregation drug effects, Probucol analogs & derivatives, Receptors, Cell Surface biosynthesis, Receptors, Cell Surface drug effects, Vascular Diseases metabolism, Vascular Diseases physiopathology
- Abstract
Oxidation-sensitive signals are important in platelet activation. The novel, phenolic, intracellular and extra-cellular antioxidant AGI-1067 inhibits the expression of a number of proinflammatory genes involved in atherosclerosis. The effect of AGI-1067 on human platelets was evaluated. Blood obtained from 20 aspirin-naïve volunteers with multiple risk factors for vascular disease was preincubated with escalating concentrations of AGI-1067 for the assessment of its ex vivo effects on platelet aggregation and expression of major surface receptors flow cytometry, evaluated by flow cytometry. AGI-1067 resulted in significant inhibition of a variety of activation-dependent platelet biomarkers in healthy volunteers, including adenosine diphosphate-induced platelet aggregation and decreased surface platelet expression of glycoprotein IIb/IIIa antigen, activity with PAC-1 antibody, and glycoprotein Ib (CD42b). The effect of AGI-1067 differs from other known antiplatelet agents, suggesting opportunities for therapeutic combination. These data need to be confirmed in subjects receiving orally dosed AGI-1067 to be clinically relevant.
- Published
- 2006
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