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Journal of Cardiovascular Pharmacology and Therapeutics
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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

Victor Serebruany, MD, PhD

HeartDrug Research Laboratories, Johns Hopkins University Baltimore, Maryland, Heartdrug{at}aol.com

Alex Malinin, MD

HeartDrug Research Laboratories, Johns Hopkins University Baltimore, Maryland

Robert Scott, MD

AtheroGenics Inc, Alpharetta, Georgia

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.

Key Words: antioxidants • coronary artery disease • platelets

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 3, 191-196 (2006)
DOI: 10.1177/1074248406290598
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