TY - JOUR
T1 - 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
AU - Serebruany, Victor
AU - Malinin, Alex
AU - Scott, Robert
PY - 2006/9
Y1 - 2006/9
N2 - Oxidation-sensitive signals are important in platelet activation. The novel, phenolic, intracellular and extracellular 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.
AB - Oxidation-sensitive signals are important in platelet activation. The novel, phenolic, intracellular and extracellular 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.
KW - Antioxidants
KW - Coronary artery disease
KW - Platelets
UR - http://www.scopus.com/inward/record.url?scp=33749574567&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749574567&partnerID=8YFLogxK
U2 - 10.1177/1074248406290598
DO - 10.1177/1074248406290598
M3 - Article
C2 - 17056832
AN - SCOPUS:33749574567
SN - 1074-2484
VL - 11
SP - 191
EP - 196
JO - Journal of Cardiovascular Pharmacology and Therapeutics
JF - Journal of Cardiovascular Pharmacology and Therapeutics
IS - 3
ER -