Sequential morphologic studies of regression of advanced atherosclerosis.

Atherosclerosis produced in the abdominal aortas of swine by balloon injury and six-month feeding of a high-cholesterol diet resulted in a spectrum of lesions that varied, by gross and/or microscopic examination, from early nonelevated fatty streaks to markedly advanced necrotic and calcified atheromas. On gross examination, the flat lesions had disappeared within five months on the regression regimen, while the advanced lesions persisted after 14 months of withdrawal of the dietary stimulus. Microscopically, the advanced lesions showed changes compatible with a healing process, with a virtual disappearance of foam cells, a marked decrease in necrosis, and replacement of necrotic debris by fibrous tissue and calcification that increased during the regression period. In the early phase of the regression process, the decrease in the number of foam cells was accompanied by an increase in the number of macrophages. The latter cells were found to be closely associated with necrosis, which suggests that macrophages may play a role in the removal of necrotic debris. These results, together with those of our previous experiment on regression of less advanced lesions, suggest that the rate and degree of regression of an atheroma may be a function of its severity.