Matthew D Linden PhD andMark I Furman MD

Contents

Introduction

Molecular Basis of Monocyte-Platelet Interaction Monocyte-Platelet Aggregates as a Marker of CAD Laboratory Detection of Monocyte-Platelet Aggregation Pathophysiology of Monocyte-Platelet Aggregates in CAD Conclusion References

Summary

Platelets are a central cellular interface of the thrombotic and inflammatory processes of coronary atherosclerosis and modulate this interface by binding to leukocytes and altering their function. In addition, platelet activation; formation of leukocyte-platelet aggregates (monocyte-platelet aggregates and neutrophil-platelet aggregates); and platelet secretion of inflammatory modulators that affect leukocyte function, such as CD40 ligand, are associated with progression of disease across the entire spectrum of atherothrombosis. Monocyte-platelet aggregates are elevated in stable coronary artery disease and further elevate with plaque rupture, characteristic of percutaneous coronary intervention, acute coronary syndromes, and myocardial infarction. Through this interaction, activated platelets may contribute to the pathogensis of ischemic heart disease by localizing and activating monocytes to the site of the atherosclerotic lesion. These heterotypic aggregates have potential for a number of clinical applications, including measurement as an early marker for plaque rupture, evaluation of the efficacy of antiplatelet therapy, and as a potential target for therapeutic intervention. Additional investigations evaluating these applications as well as the relationship between monocyte-platelet aggregates and outcome are needed.

Key Words: Unstable angina; acute coronary syndrome; platelets; monocytes.

From: Contemporary Cardiology: Cardiovascular Biomarkers: Pathophysiology and Disease Management Edited by: David A. Morrow © Humana Press Inc., Totowa, NJ

Fig. 1. Molecular basis of monocyte-platelet aggregates. Activated platelets express P-selectin on the cell surface. P-selectin binds to PSGL-1 constitutively expressed on monocyte. This initial adhesion causes activation of the monocyte, resulting in a conformational change and increased expression ofMac-1. Binding ofMac-1 to GPIIb-IIIa via fibrinogen, and directly to GPIba on the platelet, stabilizes the monocyte-platelet aggregate.

Fig. 1. Molecular basis of monocyte-platelet aggregates. Activated platelets express P-selectin on the cell surface. P-selectin binds to PSGL-1 constitutively expressed on monocyte. This initial adhesion causes activation of the monocyte, resulting in a conformational change and increased expression ofMac-1. Binding ofMac-1 to GPIIb-IIIa via fibrinogen, and directly to GPIba on the platelet, stabilizes the monocyte-platelet aggregate.

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