title: Effects of ubiquitin-proteasome system deregulation on the vascular senescence and atherosclerosis process in elderly patients.
abstract: BACKGROUND
  The role of the ubiquitin-proteasome system in the vascular senescence and atherosclerotic progression of elderly patients is unclear. We evaluated ubiquitin-proteasome activity in carotid plaques of asymptomatic elderly and adult patients.
  
  
  METHODS
  Plaques were obtained from 28 elderly and 18 adult patients undergoing carotid endarterectomy. Plaques were analyzed for ubiquitin levels, proteasome 20S activity, p16 and p53, nitrotyrosine, matrix metalloproteinase-9 (MMP-9) and collagen content (immunohistochemistry and enzyme-linked immunosorbent assay). Serial sections were incubated with specific antibodies anti-human leukocyte antigen (HLA)-DR, anti CD68 and anti-CD3.
  
  
  RESULTS
  Compared to plaques obtained from adult patients, plaques of elderly patients had more ubiquitin levels (257.4 +/- 118.9 ng/mg vs 110 +/- 14.4 ng/mg, p <.001), nitrotyrosine (3.8 +/- 0.55 nmol/pg vs 1.1 +/- 0.19 nmol/pg, p <.001), p53 and p16 staining (p <.01), and MMP-9 levels (14.6 +/- 2.5 microg/mg vs 3.2 +/- 0.1.8 microg/mg, p <.001), along with a lesser collagen content (21.9 +/- 4.8% vs 7.1 +/- 2.8%, p <.05) and less proteasome 20S activity (24.2 +/- 6.9 pmol/mg vs 78.4 +/- 10.3 pmol/mg, p <.001).
  
  
  CONCLUSIONS
  Our data suggest that reduction of proteasome activity promotes vascular cell senescence, thereby contributing to the pathogenesis of human atherosclerosis.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, Italy. raffaele.marfella@unina2.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Clara
authors.initials: C
authors.lastname: Di Filippo
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Laieta
authors.forename: Rosanna
authors.initials: R
authors.lastname: Vestini
authors.forename: Michelangela
authors.initials: M
authors.lastname: Barbieri
authors.forename: Paolo
authors.initials: P
authors.lastname: Sangiulo
authors.forename: Basilio
authors.initials: B
authors.lastname: Crescenzi
authors.forename: Franca
authors.initials: F
authors.lastname: Ferraraccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Michele
authors.initials: M
authors.lastname: D'Amico
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism / Q000502:physiology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004268:DNA-Binding Proteins; C478985:PDRG1 protein, human; D025801:Ubiquitin; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D046988:Proteasome Endopeptidase Complex