title: Arterial tissue and plasma concentration of enzymatic-driven oxysterols are associated with severe peripheral atherosclerotic disease and systemic inflammatory activity.
abstract: BACKGROUND
  Cholesterol undergoes oxidation via both enzymatic stress- and free radical-mediated mechanisms, generating a wide range of oxysterols. In contrast to oxidative stress-driven metabolites, enzymatic stress-derived oxysterols are scarcely studied in their association with atherosclerotic disease in humans.
  
  
  METHODS
  24S-hydroxycholesterol (24S-HC), 25-hydroxycholesterol (25-HC), and 27-hydroxycholesterol (27-HC) were assessed in plasma and arteries with atherosclerotic plaques from 10 patients (54-84 years) with severe peripheral artery disease (PAD) as well as arteries free of atherosclerotic plaques from 13 individuals (45-78 years, controls).
  
  
  RESULTS
  Plasma 25-HC was higher in PAD individuals than in controls (6.3[2] vs. 3.9[1.9] ng/mgCol; p = 0.004). 24S-HC and 27-HC levels were, respectively, five- and 20-fold higher in the arterial tissue of PAD individuals than in those of the controls (p = 0.016 and p = 0.001). Plasma C-reactive protein correlated with plasma 24-HC (r = 0.51; p = 0.010), 25-HC (r = 0.75; p < 0.001), 27-HC (r = 0.48; p = 0.015), and with tissue 24S-HC (r = 0.4; p = 0.041) and 27-HC (r = 0.46; p = 0.023).
  
  
  CONCLUSIONS
  Arterial intima accumulation of 27-HC and 24S-HC is associated with advanced atherosclerotic disease and systemic inflammatory activity in individuals with severe PAD.
authors.affiliation: Lipid Laboratory and Center for Medicine and Experimental Surgery, Faculty of Medical Sciences, University of Campinas , Campinas, SP , Brazil.
authors.forename: V W M
authors.initials: VW
authors.lastname: Virginio
authors.forename: V S
authors.initials: VS
authors.lastname: Nunes
authors.forename: F A
authors.initials: FA
authors.lastname: Moura
authors.forename: F H
authors.initials: FH
authors.lastname: Menezes
authors.forename: N A
authors.initials: NA
authors.lastname: Andreollo
authors.forename: F
authors.initials: F
authors.lastname: Rogerio
authors.forename: D Z
authors.initials: DZ
authors.lastname: Scherrer
authors.forename: E C R
authors.initials: EC
authors.lastname: Quintão
authors.forename: E
authors.initials: E
authors.lastname: Nakandakare
authors.forename: O
authors.initials: O
authors.lastname: Petrucci
authors.forename: W
authors.initials: W
authors.lastname: Nadruz-Junior
authors.forename: E C
authors.initials: EC
authors.lastname: de Faria
authors.forename: A C
authors.initials: AC
authors.lastname: Sposito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000737:chemistry*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood*
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; C007997:25-hydroxycholesterol; D002097:C-Reactive Protein
keywords: 24S-hydroxycholesterol; atherosclerosis; oxysterols; peripheral artery disease