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.
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.
Serebruany
Victor
V
HeartDrug Research Laboratories, Johns Hopkins University Baltimore, Maryland, USA. Heartdrug@aol.com
Malinin
Alex
A
Scott
Robert
R
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects; D000975:Antioxidants / Q000494:pharmacology*; D015142:Baltimore; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects; D011341:Probucol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000145:classification / Q000187:drug effects*; D012307:Risk Factors; D014652:Vascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology*
D015703:Antigens, CD; D000975:Antioxidants; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C471047:succinobucol; D011341:Probucol