Cell death in atheromatous plaque of the carotid artery occurs through necrosis rather than apoptosis.
Thrombogenic plaques associated with acute myocardial infarction and sudden cardiac death are relatively acellular but the mechanisms responsible for cell loss are uncertain. To help elucidate this, we investigated advanced atherosclerotic lesions taken from 13 carotid arteries. The number of cells detected by the technique for identifying DNA fragmentation (occurring at apoptosis and necrosis) known as terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) technique varied in arteries from 9.6% to 40.3% and was 4 times higher in plaque (26.4 +/- 2.9%) than in the adjacent media (6.0 +/- 1.3%). The majority of TUNEL+ cells (75.5 +/- 5.6%) were smooth muscle cells (SMCs) as they also reacted with antibodies to SMC alpha-actin and myosin. TUNEL+ nuclei were found in macrophages (CD68+ cells), T-cells (CD3+ cells) and neovascular endothelial cells (von Willebrand factor: vWf+ cells) as well. From 13.0% to 34.0% (24.6 +/- 1.7%) of plaque cells stained with antibody to proliferating cell nuclear antigen (PCNA) whereas the number of PNCA+ nuclei in the adjacent media was 6 times lower (4.1 +/- 0.7%). In plaques, the number of PCNA+ cells correlated with the number of TUNEL+ cells (r = .66; p < .001) but the proportion of PCNA+ SMCs was relatively low (39.1 +/- 5.2%). Electronmicroscopic examination showed the presence of cells with condensed chromatin and convoluted cell surfaces in all arteries tested and the numbers of cells exhibiting these destructive alterations varied from 15.2% to 35.5% but no cells with typical expression of apoptotic death were detected. The results obtained indicate that all vascular cell types undergo cell death, with some prevalence in locations close to the plaque core and that intimal cells die through necrosis rather than apoptosis. We speculate that the imbalance in SMC death and proliferation may lead to acellular plaque formation.
Bobryshev
Y V
YV
Surgical Professional Unit, St. Vincent's Hospital, Darlinghurst NSW, Australia. Cell Death in atheromatous plague of the carotid artery occurs through necrosis rather than apoptosis.
Babaev
V R
VR
Lord
R S
RS
Watanabe
T
T
D017209:Apoptosis; D001161:Arteriosclerosis / Q000473:pathology*; D002339:Carotid Arteries / Q000473:pathology*; D006801:Humans; D009336:Necrosis