Thrombosis:

Intravascular thrombosis is one of the most frequent pathological events and a major cause of morbidity and mortality in developed countries. Critical steps in the development of acute coronary syndromes are the development of athersclerotic plaque and the formation of partially or completely occlusive thrombi. 

The objective of our research is to evaluate the efficacy of novel platelet antagonists in inhibiting platelet responses in two flow models of platelet thrombus formation:

1. Direct platelet aggregation induced by increased stress conditions applied by a cone/plate rheometer.
2. Platelet adhesion onto sub-endothelial surfaces followed by aggregation in a perfusion system.

Moreover, our studies focus on the kinetics and molecular requirements of platelet binding to leukocyte sub-populations as a function of the dynamic shear environment.

Select Publications:

K.C. Ahn, A.J. Jun, P. Pawar, S. Jadhav, S. Napier, O.J. McCarty, K. Konstantopoulos, "Preferential binding of platelets to monocytes over neutrophils under flow." Biochem Biophys Res Commun. 329(1); 345-355, 2005. html

O.J.T. McCarty, J. P. Abulencia, S.A. Mousa and K. Konstantopoulos, “Evaluation of GPIIb/IIIa Antagonists In In-Vitro Flow Models of Thrombosis”, Methods in Molecular Medicine 93; 21-34, 2004.

O.J.T. McCarty, N. Tien, B.S. Bochner, K. Konstantopoulos, “Exogenous Eosinophil Activation Converts PSGL-1-Dependent Binding to CD18-Dependent Stable Adhesion to Platelets in Shear Flow” American Journal of Physiology Cell Physiology 284(5); C1223-1234, 2003. html

S.A. Mousa, J. P. Abulencia, O.J.T. McCarty, N.A. Turner, K. Konstantopoulos, “Comparative Efficacy Between the GPIIb/IIIa Antagonists, Roxifiban and Orbofiban, in Inhibiting Platelet Function in Flow Models of Thrombosis”, Journal of Cardiovascular Pharmacology 39; 552-560, 2002. html

S.A. Mousa, K. Konstantopoulos, R. Giugliano, “Oral Antiplatelet Therapies Beyond Aspirin and Thienopyridines, Therapeutic Agents for Thrombosis and Thrombolysis: Second Edition (A. Sasahara & J. Loscalzo, eds.), Marcel Dekker, Inc., New York, NY. pp. 451-476, 2002.

J. P. Abulencia, N. Tien, O.J.T. McCarty, D. Plymire, S.A. Mousa, K. Konstantopoulos, “Comparative Antiplatelet Efficacy of a Novel Nonpeptide GPIIb/IIIa Antagonist (XV454) and Abciximab (c7E3) in Flow Models of Thrombosis”, Arterioscler Thromb & Vasc Biol. 21(1); 149-156, 2001. html

K. Konstantopoulos and S.A. Mousa, “Antiplatelet Therapies: Platelet GPIIb/IIIa Antagonists & Beyond” Current Opinion in Investigational Drugs 2(8); 1086-1092, 2001

 

Three-dimensional computer-generated color representations (from videotape of real-time data) of platelet adhesion and subsequent aggregation on collagen I/von Willebrand factor from normal heparinized blood (in the absence or presence of a GPIIb-IIIa antagonist, XV454) perfused at 37 °C for 1 min at 1,500 sec-1.