Decreased paraoxonase-2 expression in human carotids during the progression of atherosclerosis.
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.
Fortunato
Giuliana
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via S. Pansini 5, 80131 Napoli, Italy.
Di Taranto
Maria Donata
MD
Bracale
Umberto Marcello
UM
Del Guercio
Luca
L
Carbone
Francesca
F
Mazzaccara
Cristina
C
Morgante
Alberto
A
D'Armiento
Francesco Paolo
FP
D'Armiento
Maria
M
Porcellini
Massimo
M
Sacchetti
Lucia
L
Bracale
Giancarlo
G
Salvatore
Francesco
F
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
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