title: Apoptosis in human atherosclerosis and restenosis.
abstract: BACKGROUND
  Apoptosis has been recognized in normal, including rapidly proliferating, cell populations and is inferred to be potentially responsible for the maintenance of stable cell numbers in tissues with various degrees of proliferative activity. Previous studies performed in rats indicated that despite the persistence of a relatively high level of injury-induced proliferative activity, total arterial smooth muscle content at 12 weeks remained unchanged from that measured at 2 weeks, suggesting that accrual of vascular smooth muscle cells is mitigated by cell death. The extent to which apoptosis may be observed in human atherosclerosis and/or restenosis, however, has not been previously established.
  
  
  RESULTS
  We performed immunohistochemical studies on 56 specimens retrieved from patients undergoing directional atherectomy for primary atherosclerotic lesions or recurrent arterial narrowing after percutaneous revascularization (restenosis). Immunohistochemical staining disclosed evidence of apoptosis in 35 (63%) of the 56 specimens studied. When present, immunohistochemical evidence of apoptosis was typically limited to < 2% of cells in the specimen. The finding of apoptosis, however, was not distributed equally among four groups of specimens studied. Specimens retrieved from patients with restenosis were more frequently observed to contain foci of apoptosis than specimens retrieved from patients with primary atherosclerotic lesions. Among 14 peripheral arterial specimens from patients with restenosis, 13 (93%) contained foci of apoptosis; in contrast, apoptosis was observed in only 6 (43%) of 14 peripheral specimens from patients with primary lesions (P = .0046). Among coronary arterial specimens, apoptosis was observed in 12 (86%) of 14 specimens from patients with restenosis versus 6 (29%) of 14 specimens from patients with primary obstructions (P < .0075).
  
  
  CONCLUSIONS
  Apoptosis is a feature of human vascular pathology, including restenotic lesions and, to a lesser extent, primary atherosclerotic lesions. The findings of the present study suggest that apoptosis may modulate the cellularity of lesions that produce human vascular obstruction, particularly those with evidence of more extensive proliferative activity.
authors.affiliation: Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
authors.forename: M
authors.initials: M
authors.lastname: Kearney
authors.forename: S
authors.initials: S
authors.lastname: Bortman
authors.forename: J
authors.initials: J
authors.lastname: Passeri
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D017073:Atherectomy; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology / Q000502:physiology; D003251:Constriction, Pathologic / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2; D012008:Recurrence; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019204:GTP-Binding Proteins