Transitional features in human atherosclerosis. Intimal thickening, cholesterol clefts, and cell loss in human aortic...

The possible transition from a subset of fatty streaks to fibrous plaques in human atherosclerosis has long been postulated, but transitional features in lesions have rarely been demonstrated. We examined human aortic fatty streaks to determine whether significant tendencies toward intimal thickening and toward deep extracellular lipid deposition might be found. To provide accurate ultrastructural assessment of lipid, tissues were processed by new electron microscopic cytochemical techniques. Unilateral fatty streaks exhibited a 60% increase in intimal thickness when compared to contralateral control tissue. Fat droplets in intimal cells accounted for approximately half of the increase; nonfat portions of cells and extracellular matrix accounted for the remainder. Six of 32 fatty streaks (19%) contained cholesterol clefts, which were found in the musculo-elastic (deep) layer of the intima or in the tunica media. Volume fractions occupied by cells in deep intima were reduced when cholesterol clefts were evident, suggesting loss of cells in early core regions. Light and electron microscopy showed structures consistent with lipid-rich core regions in lesions with cholesterol clefts and in a few lesions without cholesterol clefts. The findings of intimal thickening, core region formation, and disappearance of intimal cells constitute new evidence that some fatty streaks are progressive lesions and sites of eventual fibrous plaque development. The findings also suggest that the lipid-rich core region does not originate primarily from the debris of dead foam cells in the superficial intima, but instead arises from lipids accumulating gradually in the extracellular matrix of the deep intima.