title: Apoptosis and related proteins in different stages of human atherosclerotic plaques.
abstract: BACKGROUND
  The transition of a fatty streak into an atherosclerotic plaque is characterized by the appearance of focal and diffuse regions of cell death. We have investigated the distribution of apoptotic cell death and apoptosis-related proteins in early and advanced atherosclerotic lesions.
  
  
  RESULTS
  Human atherosclerotic plaques were studied by whole-mount carotid endarterectomy specimens (n=18). This approach allowed comparison of adaptive intimal thickenings, fatty streaks, and advanced atherosclerotic plaques of the same patient. The fatty streaks differed from adaptive intimal thickenings by the presence of BAX (P<0.01), a proapoptotic protein of the BCL-2 family. Both regions were composed mainly of smooth muscle cells (SMCs), and macrophage infiltration was low and not different. Apoptosis, as detected by DNA in situ end labeling (terminal deoxynucleotidyl transferase end labeling [TUNEL] and in situ nick translation) was not present in these regions. Apoptosis of SMCs and macrophages, however, was present in advanced atherosclerotic plaques that were present mainly in the carotid sinus. A dense infiltration of macrophages (5.8+/-3% surface area) was present in these advanced atherosclerotic plaques. Cytoplasmic remnants of apoptotic SMCs, enclosed by a cage of thickened basal lamina, were TUNEL negative and remained present in the plaques as matrix vesicles.
  
  
  CONCLUSIONS
  We conclude that SMCs within human fatty streaks express BAX, which increases the susceptibility of these cells to undergo apoptosis. The localization of these susceptible SMCs in the deep layer of the fatty streaks could be important in our understanding of the transition of fatty streaks into atherosclerotic plaques, which are characterized by regions of cell death. Matrix vesicles are BAX-immunoreactive cytoplasmic remnants of fragmented SMCs that can calcify and may be considered the graves of SMCs that have died in the plaques.
authors.affiliation: Department of Pathology, A.Z. Middelheim, Antwerp, Belgium. mark.kockx@uia.ua.ac.be
authors.forename: M M
authors.initials: MM
authors.lastname: Kockx
authors.forename: G R
authors.initials: GR
authors.lastname: De Meyer
authors.forename: J
authors.initials: J
authors.lastname: Muhring
authors.forename: W
authors.initials: W
authors.lastname: Jacob
authors.forename: H
authors.initials: H
authors.lastname: Bult
authors.forename: A G
authors.initials: AG
authors.lastname: Herman
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001161:Arteriosclerosis / Q000473:pathology*; D001710:Biotin; D002340:Carotid Artery Diseases / Q000473:pathology*; D002784:Cholesterol / Q000032:analysis; D053938:DNA Fragmentation; D003856:Deoxyuracil Nucleotides; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D006801:Humans; D008264:Macrophages; D008297:Male; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D013194:Staining and Labeling; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology / Q000648:ultrastructure
chemical_list: D003856:Deoxyuracil Nucleotides; D005227:Fatty Acids; D019253:Proto-Oncogene Proteins c-bcl-2; D001710:Biotin; D002784:Cholesterol