Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease

Abstract

Atherosclerosis is the underlying reason for nearly all causes of coronary artery disease and peripheral arterial disease and many cases of stroke. Atherosclerosis is a systemic inflammatory process characterised by the accumulation of lipids and macrophages/lymphocytes within the intima of large arteries. The deposition of these blood borne materials and the subsequent thickening of the wall often significantly compromise the residual lumen leading to ischaemic events distal to the arterial stenosis. However, these initial fatty streak lesions may also evolve into vulnerable plaques susceptible to rupture or erosion. Plaque disruption initiates both platelet adhesion and aggregation on the exposed vascular surface and the activation of the clotting cascade leading to the so-called atherothrombotic process. Yet, platelets have also been shown to be transporters of regulatory molecules (micro-RNA), to drive the inflammatory response and mediate atherosclerosis progression. Here we discuss our current understanding of the pathophysiological mechanisms involved in atherogenesis - from fatty streaks to complex and vulnerable atheromas - and highlight the molecular machinery used by platelets to regulate the atherogenic process, thrombosis and its clinical implications.

Keywords: Atherosclerosis; platelets; thrombosis; vulnerable atherosclerotic plaque.

Figure 1.

Antithrombotic properties of the healthy vascular endothelium. PGI₂, prostacyclin; NO, nitric oxide; ATIII, antithrombin III; ADP, adenosine diphosphate

Figure 2.

Molecules released from activated platelets. miRNA, micro-RNAs; PECAM-1, platelet endothelial cellular adhesion molecule-type 1; vWF, von Willebrand factor; RANTES, regulated on activation normal T-cell expressed and secreted; ENA-78, epithelial cell-derived neutrophil-activating peptide 78; ADP, adenosine diphosphate; ATP: adenosine triphosphate; GDT, guanosine diphosphate; GTP, guanosine triphosphate.

Figure 3.

Diagram of platelet, coagulation, and vessel-related mechanisms involved in platelet adhesion, activation and further aggregation. PAF, platelet activating factor; VWF, Von Willebrand Factor; TXA2, thromboxane A2; AA, arachidonic acid; PG, prostaglandin; ATP, adenosine triphosphate; ADP, adenosine diphosphate; TF, tissue factor; PAR, protease-activated–receptor; PC, protein C; TP, thromboxane receptors; PG, prostaglandin.

Figure 4.

Coagulation and fibrinolytic pathways. HMWK, high molecular weight kininogen; TF, tissue factor; TFPI, tissue factor pathway inhibitor; FPA, fibrinopeptide A; FPB, fibrinopeptide B; FDP, fibrin degradation products; t-PA, tissue plasminogen activator; u-PA, urokinase plasminogen activator; PAI-1, plaminogen activator inhibitor type-1.

Figure 5.

Antiplatelet agents currently used in the clinical setting, under clinical testing and under development.

Figure 6.

Natural inhibitors of coagulation and anticoagulant drugs. TF, tissue factor; VKA, vitamin K antagonists; AT, antithrombin; APC, activated protein C; TFPI, tissue factor pathway inhibitor type-1.