11 - Platelets in the pathogenesis of vascular disease and their role as a therapeutic target

Summary

INTRODUCTION

Platelets are key blood components with a physiological role in the initiation of endogenous haemostasis and effective endothelial repair following vascular injury. Platelets are responsible for the initiation of a series of complex interactions culminating in platelet aggregation and thrombus formation. As such, key platelet functions, such as adherence, activation, aggregation and interaction with coagulation factors, operate in the context of a complex and balanced interplay of receptors and mediators that ensure this process is controlled and specifically targeted to areas of vascular injury. However, in disease states, such as atherosclerosis, the abnormal initiation of platelet functions also contributes to the pathogenesis and propagation of vascular disease. Consequently, targeted therapeutic inhibition of platelets has demonstrated an important clinical role in situations of both pathological and iatrogenic vascular injury, such as atherosclerosis and angioplasty. This chapter will firstly outline the relevant platelet receptors, their agonists and other important structural platelet components and their role in platelet function. Secondly, it will outline the role of these functions in the pathogenesis and propagation of vascular disease. Finally, the mechanism of therapeutic anti-platelet agents will be reviewed along with a description of currently used methods to assess platelet function.

PLATELET FUNCTION – ADHESION AND ACTIVATION

Platelets are enucleated cytoplasmic fragments of bone marrow megakaryocytes with a limited capacity for protein synthesis. Although lacking DNA, platelets do contain megakarocyte mRNA along with components necessary for protein synthesis, and are capable of performing nuclear functions such as pre-RNA splicing.