4 - Mechanisms of plaque rupture

Summary

INTRODUCTION

Atherosclerosis continues to cause considerable morbidity and mortality, particularly in the western world. While risk factors have been clearly identified, their precise roles in early atherogenesis are complex. The early development of the plaque is dependent upon interactions between damaged endothelial cells, vessel wall smooth muscle cells and circulating inflammatory cells mediated by the release of cytokines, growth factors and cell adhesion molecules. Plaque formation may represent a cell-mediated immune phenomenon, with a variety of potential antigenic agents identified. Shear stress and flow considerations also play a part.

Atherosclerosis begins in childhood, but it takes decades for atherosclerosis to evolve into the mature plaques responsible for the onset of ischaemic symptoms. Whilst plaque growth due to smooth muscle cell proliferation, matrix synthesis and lipid accumulation may narrow the arterial lumen and ultimately limit blood flow, uncomplicated atherosclerosis is essentially a benign disease. The final clinical outcome depends on whether a plaque becomes unstable, leading to acute disruption of its surface and exposure of its thrombogenic core to the luminal blood flow. The concept of a ‘vulnerable plaque’ was initially described in 1990 and though this initially gained wide acceptance, many authors now favour the broader concept of a ‘vulnerable patient”, whereby certain systemic and haematological conditions (e.g. relative hypercaogulability) must also be met before plaque rupture will result in symptomatic thrombosis.

Mature atherosclerotic plaques are composed of a lipid core that is separated from the vessel lumen by a cap composed of fibrillar collagen.