title: Endothelial apoptosis does not determine symptom status in carotid artery disease.
abstract: BACKGROUND
  We examined the hypothesis that endothelial denudation in advanced carotid plaques (CPs) occurs by increased apoptosis of endothelial cells (ECs) using scanning electron microscopy (SEM) as well as markers of cellular proliferation and apoptosis in advanced symptomatic CPs (SCPs) and asymptomatic CPs (ACPs).
  
  
  METHODS
  93 consecutive patients underwent carotid endarterectomy. Five additional specimens were studied by SEM. We performed TUNEL assays, and immunostaining against Fas receptor (FasR), Fas ligand (FasL), activated caspase 3 (ACA3) and Ki-67.
  
  
  RESULTS
  SEM revealed morphological changes consistent with EC detachment. Surprisingly, ACA3 positivity was more pronounced on the endothelium of ACPs (4.6 +/- 0.7% of total EC count) than on SCPs (3.3 +/- 0.7%, p = 0.049), and was found to correlate positively with nuclear Ki-67 expression (r(s) = 0.275, p = 0.040). FasL expression was significantly increased on the endothelium of SCPs compared with ACPs (66.4 +/- 4.4 vs. 53.9 +/- 4.5%, p = 0.047).
  
  
  CONCLUSIONS
  Absence of increased positivity of apoptotic markers dismisses apoptosis as a dominant mechanism underlying endothelial detachment of SCPs. Rather, increased ACA3 with co-expression of Ki-67 in ACPs might suggest that renewal of endothelium by active cell turnover may contribute to clinically silent evolution of plaques with preserved EC integrity. These observations may assist in designing novel therapies to prevent endothelial decay and symptom generation in advanced carotid artery disease.
authors.affiliation: Neuroscience Program, Biomedicum Helsinki, Helsinki, Finland. Krista.Nuotio@helsinki.fi
authors.forename: Krista
authors.initials: K
authors.lastname: Nuotio
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Mäyränpää
authors.forename: Jani
authors.initials: J
authors.lastname: Saksi
authors.forename: Petra
authors.initials: P
authors.lastname: Ijas
authors.forename: Tiina
authors.initials: T
authors.lastname: Sairanen
authors.forename: Olli
authors.initials: O
authors.lastname: Carpén
authors.forename: Lauri
authors.initials: L
authors.lastname: Soinne
authors.forename: Eija
authors.initials: E
authors.lastname: Saimanen
authors.forename: Oili
authors.initials: O
authors.lastname: Salonen
authors.forename: Mauri
authors.initials: M
authors.lastname: Lepäntalo
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.forename: Perttu J
authors.initials: PJ
authors.lastname: Lindsberg
mesh_terms: D000368:Aged; D017209:Apoptosis; D002343:Carotid Artery, Internal / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D016893:Carotid Stenosis / Q000201:enzymology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D053148:Caspase 3 / Q000032:analysis; D002448:Cell Adhesion; D016894:Endarterectomy, Carotid; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology* / Q000648:ultrastructure; D053222:Fas Ligand Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D019014:fas Receptor / Q000032:analysis
chemical_list: D053222:Fas Ligand Protein; D019394:Ki-67 Antigen; D019014:fas Receptor; D053148:Caspase 3