Critical sequences of phenomena in the progression of atherosclerotic lesions, with reference to the role of microvessels

Abstract Atherosclerosis affects the inner layers of human arteries, and causes major problems by blocking, directly or indirectly, the flow of blood. This paper concerns the growth of atherosclerotic lesions (atherogenesis), in particular potential factors that may allow a form of ‘positive feedback’ that drives the development of lesions, and considers the role of microvessels. The lesions of atherosclerosis have previously been compared to, or thought of as, sites of inflammation, and involve the accumulation of cells, including large lipid-containing macrophages, and extracellular elements. In tissues other than arteries inflammation may involve, amongst other phenomena, a resolution stage with the removal or departure of macrophages via lymphatics. However, the inner aspects of large arteries do not normally demonstrate lymphatics or other microvessels, and there is evidence from animal work that the lack of vessels effectively contributes to the development of atherosclerosis, as this limits the egress of macrophages and other elements. Conversely, in humans microvessels have been suggested to play a key role in the progress of atherosclerotic lesions. The importance of microvessels is herein considered, in particular the potentially paradoxical situation where as stated the lack of microvessels can be considered to allow atherosclerosis, but on the other hand these structures are involved in lesion development – the explanation can be seen to relate to the relatively short length of time which is assessable in animal models, compared to the lengthy period over which lesions appear to develop in humans. In addition, consideration is given to other factors, including haemodynamic factors related to the physical presence of lesions, which could lead to phenomena that can be regarded as a vicious cycle of events that lead to growth of the lesion. Specifically initial inflammation may lead to scarring and anatomical distortion, which through haemodynamic and physical factors leads to more damage, more inflammation and scarring, and so on.