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.

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.
Authors	Victor Serebruany, Alex Malinin, Robert Scott
Journal	Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 11 Issue 3 Pg. 191-6 (Sep 2006) ISSN: 1074-2484 [Print] United States
PMID	17056832 (Publication Type: Journal Article)
Chemical References	Antigens, CD Antioxidants Biomarkers Cell Adhesion Molecules Platelet Membrane Glycoproteins Receptors, Cell Surface succinobucol Probucol
Topics	Adult Antigens, CD (biosynthesis, drug effects) Antioxidants (pharmacology) Baltimore Biomarkers (blood) Blood Platelets (drug effects, metabolism) Cell Adhesion Molecules (biosynthesis, drug effects) Female Flow Cytometry Humans Linear Models Male Middle Aged Platelet Aggregation (drug effects) Platelet Membrane Glycoproteins (biosynthesis, drug effects) Probucol (analogs & derivatives, pharmacology) Receptors, Cell Surface (biosynthesis, classification, drug effects) Risk Factors Vascular Diseases (epidemiology, metabolism, physiopathology)

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