Atherogenesis: Initiating Factors

This symposium on mechanisms in the development of early atheroma was held at the Ciba Foundation in London, July 5-6, 1972. For American students of atherosclerosis it differs both in the composition of the panel and in the selection of areas discussed. Only three of the 22 participants are from the United States. Eleven are from the United Kingdom, three from elsewhere in Europe, three from Israel and two from Australia. The objective has been to bring together biochemists, physicists, physiologists and clinicians to consider factors that result in the early atheromatous plaque. The body of the symposium, under the enlightened chairmanship of Sir James Lighthill, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, consists of 10 meritorious scientific presentations together with relevant discussions. As background C. W. M. Adams of London lucidly sets the morphological stage, and Elspeth Smith, Aberdeen, presents her well-known observations on chemical-morphological relations of lipids in the human intima. The symposium now progresses to less explored and more specialized fields. J. M. Bailey, Washington, DC, discusses the regulation of cell cholesterol content, focussing on the interrelated process of uptake and excretion, and on de novo biosynthesis. The scene then shifts to an area of current interest, the response of the arterial wall to mechanical stresses exerted on the vessel lining by the adjacent blood flow. D. L. Fry, Bethesda, in animal experiments finds an increased transendothelial protein influx, increased intimal fibromuscular hyperplasia and increased lipid deposition. Also connective tissue cells are shown to orient themselves along the lines of unidirectional stress. Time factors are important here. Juxtaposed is the paper by C. G. Caro, London, who has studied the topography of human atheromatous lesions. He believes that their location indicates that they occur where wall shear rate is expected to be low. This is contrary to evidence of others associating high shear and the development of lesions in cholesterol-fed animals. Caro proposes that in man the lipid accumulation in early plaques may be a matter of egress control associated with low shear rather than ingress. He studies in detail the movement of material between blood and arterial wall as influenced by diffusion boundary layers, by uptake processes at the wall itself and by subsequent transport in the intima. Returning to the molecular biochemists, Y. and 0. Stein of Jersulem, utilizing radioautographic and aortic perfusion techniques, have studied synthesis and transport pathways in the vessel wall for phospholipids, triglycerides and cholesterol esters. Also the uptake and transport of various classes of liproteins through endothelium and intima have been investigated. It is tentatively concluded that in normal