1.Role of G protein signaling in the formation of the fibrin(ogen)-integrin αIIbβ3-actin cytoskeleton complex in platelets.
Budnik I1,2, Shenkman B3, Savion N1. Platelets. 2016 Mar 30:1-13. [Epub ahead of print]
Effective platelet function requires formation of a physical link between fibrin(ogen), integrin αIIbβ3, and cytoplasmic actin filaments. We investigated the role of the Gαq, Gαi, and Gα12/13 families of heterotrimeric GTP-binding proteins (G proteins) in the assembly of a ligand-αIIbβ3-actin cytoskeleton complex. Selective and combined activation of the G proteins was achieved by using combinations of various platelet agonists and inhibitors. Formation and stability of fibrinogen-αIIbβ3 interaction were evaluated by the extent of platelet aggregation and the rate of eptifibatide-induced platelet disaggregation; association of αIIbβ3 with the cytoskeleton was analyzed by western blot. Formation of the fibrin-αIIbβ3-actin cytoskeleton complex was evaluated by rotational thromboelastometry assay in which clot formation was induced by the mixture of reptilase and factor XIIIa. We demonstrated that involvement of heterotrimeric G proteins in the formation of the ligand-αIIbβ3-cytoskeleton complex depends on whether fibrinogen or fibrin serves as the integrin ligand.
2.Eptifibatide infusion versus placebo in high risk patients with non-ST segment elevation acute coronary syndromes managed with urgent coronary artery bypass graft surgery. A prospective multicenter randomized placebo-controlled clinical trial.
Wilczynski M1, Wybraniec MT, Milewski K, Sanak M, Wita K, Buldak Ł, Kondys M, Buszman P, Bochenek A. J Cardiovasc Surg (Torino). 2016 Feb;57(1):100-10.
BACKGROUND: This randomized prospective clinical trial aimed to evaluate safety and efficacy of preoperative use of eptifibatide in high risk patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), requiring urgent coronary artery bypass graft surgery (CABG).
3.Gene mutations of platelet glycoproteins and response to tirofiban in acute coronary syndrome.
Mansur AP1, Roggerio A1, Takada JY2, Caribé PM2, Avakian SD2, Strunz CM2. Sao Paulo Med J. 2016 Jan 19. pii: S1516-31802016005001103. [Epub ahead of print]
CONTEXT AND OBJECTIVES: Glycoprotein inhibitors (abciximab, eptifibatide and tirofiban) are used in patients with unstable angina and non-ST-segment elevation myocardial infarction before percutaneous coronary intervention. Of these, tirofiban is the least effective. We hypothesized that the response to tirofiban might be associated with glycoprotein gene mutations.
4.Functional assay of antiplatelet drugs based on margination of platelets in flowing blood.
Eichinger CD1, Fogelson AL2, Hlady V1. Biointerphases. 2016 Jun 30;11(2):029805. doi: 10.1116/1.4945305.
A novel functional assay of antiplatelet drug efficacy was designed by utilizing the phenomena of platelet margination in flowing blood and transient platelet contacts with surface-immobilized platelet agonists. Flow margination enhances transient contacts of platelets with the walls of flow chambers covered with surface-immobilized proteins. Depending on the type and the surface density of the immobilized agonists, such transient interactions could "prime" the marginated platelet subpopulation for enhanced activation and adhesion downstream. By creating an upstream surface patch with an immobilized platelet agonist, platelet flow margination was used to test how effective antiplatelet drugs are in suppressing downstream platelet activation and adhesion. The platelet adhesion downstream was measured by a so-called "capture" patch region close to the distal end of the flow chamber. Platelet adhesion downstream was found to be dose-dependent on the upstream surface coverage of the "priming" patch, with immobilized fibrinogen acting as a platelet agonist.