CELL-DEATH IN HUMAN ATHEROSCLEROTIC PLAQUES INVOLVES BOTH ONCOSIS ANDAPOPTOSIS

The aim of the present study was to analyze the frequency and mechanis m of cell death in atherosclerotic plaques with a recent history ( < 6 months) of rupture. Atherosclerotic plaques were obtained from patien ts with symptomatic ipsilateral carotid stenosis > 70% diameter reduct ion undergoing carotid endarterectomy. In situ tailing and nick transl ation of fragmented DNA, agarose gel electrophoresis of plaque DNA and electron microscopy were used to identify cell death by apoptosis (pr ogrammed cell death) and oncosis. The mean number of cells containing fragmented DNA in the plaques was 12.7 +/- 3.5% (n = 15). Focal accumu lations of cells with DNA fragmentation occurred in the fibrous cap, a t sites of rupture, close to lipid deposits and necrosis and was alway s accompanied by the presence of inflammatory cells, Electrophoretic s eparation of DNA isolated from part of plaques, where the presence of DNA fragmentation had previously been demonstrated by in situ DNA nick translation, resulted in multiple ladders of 180-200 base pairs chara cteristic of apoptosis. Electron microscopic analysis revealed presenc e of cells with morphological signs of degeneration in a frequency eve n higher than that found by in situ nick translation. Some of these ce lls had a characteristic apoptotic appearance with condensed chromatin and cytoplasm, but the large majority of the cells had an ultrastruct ure typical for cells undergoing cell death by oncosis with membrane d isruption and swollen, disintegrating organelles. Thus, although apopt osis clearly takes place in atherosclerotic plaques, oncosis appears t o be a much more common mechanism for cell death. (C) 1997 Elsevier Sc ience Ireland Ltd.