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Until recently, atherosclerosis was thought of as a degenerative, slowly progressive disease, predominantly affecting the elderly, and causing symptoms through its mechanical effects on blood flow, particularly in the small calibre arteries supplying the myocardium and brain. Thus the approach to treatment has traditionally been surgical and focused on the largest and most visible or symptomatic lesions, coupled with a somewhat nihilistic belief that there was little likelihood of medical management affecting such a longstanding “end stage” process. However, recent research into the cellular and molecular events underlying the development and progression of atherosclerosis, prompted by careful descriptive studies of the underlying pathology, has shown that atherosclerosis is a dynamic, inflammatory process that is eminently modifiable. Support for this view comes from clinical trials of lipid lowering agents, particularly the “statins”, which have shown only minor effects on the size of existing lesions, but major reductions in clinical events caused by plaque rupture, implying a beneficial stabilising effect on plaque composition. This calls for a change from a quantitative (how many and how tight are the stenoses?) to a more qualitative (how active are the plaques we cannot see?) approach to atherosclerosis. Also, a better understanding of the molecular and cellular basis of atherosclerosis will inevitably lead to the design of better diagnostic and therapeutic approaches. The purpose of this review is to summarise current understanding of the pathogenesis and progression of atherosclerosis with particular reference to potential new diagnostic or therapeutic approaches.
The atherosclerotic plaque
Atherosclerosis begins as a subendothelial accumulation of lipid laden, monocyte derived foam cells and associated T cells which form a non-stenotic fatty streak. With progression, the lesions take the form of an acellular core of cholesterol esters bounded by an endothelialised fibrous cap containing vascular smooth muscle cells (VSMC) and inflammatory cells, predominantly macrophages with some …