APOPTOSIS IS ABUNDANT IN HUMAN ATHEROSCLEROTIC LESIONS, ESPECIALLY ININFLAMMATORY CELLS (MACROPHAGES AND T-CELLS), AND MAY CONTRIBUTE TO THE ACCUMULATION OF GRUEL AND PLAQUE INSTABILITY

Death of intimal tissue may bad to plaque rupture with thrombosis, whi ch is the basis of the most severe clinical consequences of atheroscle rosis. Little is known about the mechanisms that promote intimal cell death or its nature. This work was undertaken to elucidate the extent to which, the cell types in which, and where programmed cell death, ap optosis, might occur in atherosclerotic lesions. The material was fibr ous or fibro-fatty non-ulcerated lesions from the human thoracic aorta and coronary arteries. Apoptosis was indicated by the in situ labelin g of internucleosomally degraded DNA with the TUNEL technique, which h as a preference for apoptosis as compared with cell necrosis and was c ombined with the immunohistochemical typing of cells. Apoptosis was co rroborated by morphological criteria on the light and electron microsc ope levels and by the presence of an apoptosis-specific protein. It wa s common in the lesions and virtually absent in non-atherosclerotic re gions. It occurred in smooth muscle cells subendothelially, in places of the fibrous cap, and in the underlying media, which may destabilize the plaque and promote rupture. Inflammatory cells, ie, macrophages a nd T cells, appeared abundantly subendothelially, in the fibrous cap, and in the shoulder regions, and apoptosis was common, maybe reflectin g a means for quenching of the inflammatory reaction. Many macrophages contained abundant apoptotic material indicative of phagocytosis of a poptotic cells, but the occurrence of apoptosis, even in some of these cells, and of apoptotic material extracellularly and the very high nu mbers of apoptotic cells that were encountered may indicate insufficie nt mechanisms for the removal of apoptotic cells fn the atheroscleroti c lesion. It is not possible to decide as yet whether this is due to o verloading with cellular material by inflammation and cell multiplicat ion, to an increased frequency of apoptosis, to a reduction of the rem oval/degradation of apoptotic material by macrophages, or a combinatio n of these factors.