title: Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) is a complex multi-factorial disease with life-threatening complications. AAA is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in AAA pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with AAA in comparison with matched controls.
  
  
  METHODS
  TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG).
  
  
  CONCLUSIONS
  Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from AAA patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from AAA patients compared to matched controls. Increased DNA double strand breaks were detected in AAA patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from AAA patients. This study shows for the first time that EC and VSMC from AAA have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.
authors.affiliation: Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cafueri
authors.forename: Federica
authors.initials: F
authors.lastname: Parodi
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.forename: Maria
authors.initials: M
authors.lastname: Bertolotto
authors.forename: Francesco
authors.initials: F
authors.lastname: Ventura
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pezzolo
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*