Symposium on causal mechanisms in atherosclerosis and thrombosis. V
Cerebral atherosclerosis in swine: Role of necrosis in progression of diet-induced lesions from proliferative to atheromatous stage1

https://doi.org/10.1016/S0014-4800(68)80004-8Get rights and content

Summary

In recent studies of the pathogenesis of atherosclerosis, we have sequentially categorized the atheroslcerotic lesions into (1) preproliferative, (2) proliferative, and (3) atheromatous phases. This report based on electron microscopy observations is mainly concerned with the cellular and subcellular events occurring in transition from the proliferative to the atheromatous phase with emphasis on the possible role of necrosis. We also paid special attention to the internal elastica, endothelial cells and smooth muscle cells of the inner media at all stages.

Materials for study consisted of middle cerebral arteries of young swine fed atherogenic or stock diet for 160 days. Atheroslcerotic lesions in these arteries appeared to be in a transitional state from the proliferative to atheromatous phase. They consisted of collections of bizarre smooth muscle cells, fibrillary and nonfibrillary materials including dissolved neutral lipids, dense and laminated phospholipids, cholesterol clefts, and fine reticulated material consistent with mucopolysaccharides. There were also cellular degenerative changes that can be classified into (1) pyknosis and karyorrhexis and (2) cytolysis, and, in addition, focal accumulation of lipid-rich debris which is the hallmark of atheroma. Viable smooth muscle cells responded by either phagocytizing or sequestering the products of cell death. Based on the transitional forms from recognizable smooth muscle cells to disintegrated products of cell death, and also on the lack of identifying features suggestive of other origin, most and perhaps all of the dead cells in the early atheromata appeared to have been smooth muscle cells and the major portion of atheromatous debris probably originated from necrosis of smooth muscle cells. Deposition of cholesterol-rich material from the extracellular fluid in the necrotic foci probably occurs as the lesion progresses, adding to the mass. The endothelial cells had changes suggestive of disturbed metabolism in both lesion and nonlesion areas perhaps leading to increased permeability, and resulting in accelerated transport of blood consituents from the lumen to deeper layers.

Although the internal elastica was well developed in the middle cerebral arteries, it often had erosion effects in the diet-induced lesions apparently leading to wide and numerous gaps with loss of sharp demarcation between the intima and media. Such erosion effects and fragmentation of internal elastica were associated with adjacent smooth muscle cells with exaggerated basement membrane.

Study of the control specimens revealed in a few instances miniature foci of degeneration and necrosis in the inner media, but without visible collections of lipid-rich debris. Although an extensive search was required to find these degenerative foci in the control inner media, the fact that they were present at all is suggestive of a precarious situation for these cells, which would make them relatively vulnerable to the effect of noxious agents.

References (22)

  • McGillH.C. et al.

    Natural history of human atherosclerotic lesions

  • Cited by (0)

    1

    Parts of this paper were presented at the Annual Meeting of the Federation of American Societies of Experimental Biology in Chicago, April, 1967.

    View full text