IS ATHEROSCLEROSIS A DISEASE OF THE OUTSIDE OF ARTERIES?

Abstract

The early stages of atherosclerosis are characterised by: (i) Intimal infiltration by macrophages, (ii) Intimal smooth muscle cell (SMC) proliferation and (iii) Accumulation of cholesterol within the vessel wall. Many studies have suggested that these changes occur subsequent to endothelial cell (EC) damage and platelet deposition. We now describe a new animal model with characteristics of early human atherosclerosis but without observable EC damage or platelet deposition. 12 rabbits were separated into 2 groups; each was fed normal laboratory chow and one group was supplemented with lg/day cholesterol. At day 0, under anaesthesia, a silastic collar (internal volume 0.3ml) was placed around the left carotid artery. The collar was filled with whole blood and sealed without causing Constriction of the vessel. The right carotid arteries were sham operated. The vessels were replaced and the animals allowed to recover. After 14 days both carotids were perfuse-fixed in situ. The left carotid arteries were separated into:(A)A mid-region from within the collar,(B)A region proximal to the collar and (C)A distal region. These regions were subdivided for histology and scanning E.M. Medial/Intimal ratios of transverse sections of each region were analysed by computerised image analysis and shown below.Histology demonstrated an intense proliferation within 14 days which resembled early atherosclerosis. There was intimal monocyte infiltration and SMC proliferation and loss of SMC from the medial layer. Scanning E.M. revealed no observable EC damage or platelet adhesion. The lesion was highly focal and generally restricted to the collar region. Dietary cholesterol did not enhance proliferation but did cause foam cell formation. Sham operated vessels showed no significant atherosclerotic changes. Thus, early atherosclerotic lesions may be the result of damage to the outer layers of blood vessels.