EVIDENCE FOR APOPTOSIS IN HUMAN ATHEROGENESIS AND IN A RAT VASCULAR INJURY MODEL

Apoptosis is a physiological cell death process important for normal d evelopment and involved in many pathological conditions In atheroscler osis, pathological accumulation of cells in the intima has been attrib uted to the migration and proliferation of smooth muscle cells, macrop hages, and lymphocytes. In this report, we explored the possibilility that apoptosis may also contribute to the pathogenesis of this disease , We examined 35 human atherosclerotic lesion samples and identified a substantial number of cells undergoing apoptosis in 25 of the samples Furthermore, in a rat vascular injury model, apoptotic cells were spe cifically identified In the neointima The presence of apoptotic cells was demonstrated by terminal deoxynucleotidyl transferase-mediated dUT P-biotin nick end labeling, nuclear staining with propidium iodide, an d electron microscopy, Immunostaining with cell-type-specific markers and subsequent terminal deoxynucleotidyl transferase-mediated dUTP-bio tin nick end labeling analysis on the same sample revealed that the ma jority of the apoptotic cells were modulated smooth muscle cells as we ll as macrophages. These results indicate that apoptosis occurs in cel ls of the injured blood vessel as well as the advanced atherosclerotic lesion and that physiological cell death may have an important role i n determining the course of atherogenesis.