title: Decreased paraoxonase-2 expression in human carotids during the progression of atherosclerosis.
abstract: OBJECTIVE
  Many gene products involved in oxidation and inflammation are implicated in the pathogenesis of atherosclerosis. We investigated paraoxonase 2 (PON2), 5-lipoxygenase (5-LO), and 5-LO activating protein (FLAP) expression and malondialdehyde (MDA) levels in carotid lesions to assess their involvement in plaque formation.
  
  
  RESULTS
  We measured gene expression and MDA levels in atherosclerotic plaques from 59 patients undergoing carotid endarterectomy, and in plaque-adjacent tissue from 41/59 patients. Twenty-three fetal carotids and 6 mammary arteries were also investigated. Real-time polymerase chain reaction and immunohistochemistry revealed decreased PON2 expression in plaques versus adjacent regions (P<0.005, P<0.001, respectively), mammary arteries (P<0.031, P<0.001, respectively), and fetal carotids (both P<0.001). mRNA levels of 5-LO and FLAP were higher (P<0.038, P<0.005, respectively) in lesions versus fetal carotids. MDA was higher in plaques versus plaque-adjacent tissue and fetal carotids. PON2 mRNA was downregulated by oxidative stress in 5 ex vivo experiments, thereby indicating its possible atheroprotection role.
  
  
  CONCLUSIONS
  We demonstrate that PON2 mRNA and protein are decreased in plaques versus plaque-adjacent tissue, mammary arteries, and fetal carotids. Our data indicate that the protective effect of PON2 could fail during atherosclerosis exacerbation; this was confirmed by the increase of MDA levels. The increase of 5-LO and FLAP mRNA expression confirms their role as inflammatory markers associated to atherosclerosis.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fortunato
authors.forename: Maria Donata
authors.initials: MD
authors.lastname: Di Taranto
authors.forename: Umberto Marcello
authors.initials: UM
authors.lastname: Bracale
authors.forename: Luca
authors.initials: L
authors.lastname: Del Guercio
authors.forename: Francesca
authors.initials: F
authors.lastname: Carbone
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzaccara
authors.forename: Alberto
authors.initials: A
authors.lastname: Morgante
authors.forename: Francesco Paolo
authors.initials: FP
authors.lastname: D'Armiento
authors.forename: Maria
authors.initials: M
authors.lastname: D'Armiento
authors.forename: Massimo
authors.initials: M
authors.lastname: Porcellini
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Bracale
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000150:complications / Q000201:enzymology*; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications / Q000201:enzymology* / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D016894:Endarterectomy, Carotid; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D046509:Tissue Culture Techniques
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D015415:Biomarkers; D002352:Carrier Proteins; D008565:Membrane Proteins; D001094:Arachidonate 5-Lipoxygenase; D043303:Aryldialkylphosphatase; C468411:PON2 protein, human