title: Lysophosphatidylcholine and carotid intima-media thickness in young smokers: a role for oxidized LDL-induced expression of PBMC lipoprotein-associated phospholipase A2?
abstract: BACKGROUND
  Although cigarette smoking has been associated with carotid intima-media thickness (CIMT) the mechanisms are yet not completely known. Lysophosphatidylcholine (lysoPC), a main product of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, appears to be a major determinant of the pro-atherogenic properties of oxidized LDL (oxLDL) and to induce proteoglycan synthesis, a main player in intimal thickening. In this study we assessed whether cigarette smoking-induced oxidative stress may influence plasma Lp-PLA2 and lysoPC and Lp-PLA2 expression in peripheral blood mononuclear cells (PBMC), as well as the relationship between lysoPC and CIMT.
  
  
  RESULTS
  45 healthy smokers and 45 age and sex-matched subjects participated in this study. Smokers, compared to non-smokers, showed increased plasma concentrations of oxLDL, Lp-PLA2 and lysoPC together with up-regulation of Lp-PLA2 (mRNA and protein) expression in PBMC (P<0.001). Plasma Lp-PLA2 positively correlated with both lysoPC (r=0.639, P<0.001) and PBMC mRNA Lp-PLA2 (r=0.484, P<0.001) in all subjects. Moreover CIMT that was higher in smokers (P<0.001), positively correlated with lysoPC (r=0.55, P<0.001). Then in in vitro study we demonstrated that both oxLDL (at concentrations similar to those found in smoker's serum) and oxidized phospholipids contained in oxLDL, were able to up-regulate mRNA Lp-PLA2 in PBMC. This effect was likely due, at least in part, to the enrichment in oxidized phospholipids found in PBMC after exposure to oxLDL. Our results also showed that in human aortic smooth muscle cells lysoPC, at concentrations similar to those found in smokers, increased the expression of biglycan and versican, two main proteoglycans.
  
  
  CONCLUSIONS
  In smokers a further effect of raised oxidative stress is the up-regulation of Lp-PLA2 expression in PBMC with subsequent increase of plasma Lp-PLA2 and lysoPC. Moreover the correlation between lysoPC and CIMT together with the finding that lysoPC up-regulates proteoglycan synthesis suggests that lysoPC may be a link between smoking and intimal thickening.
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Fratta Pasini
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Stranieri
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vallerio
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Mozzini
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Solani
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Cominacini
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cominacini
authors.affiliation: Section of Internal Medicine D, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Ulisse
authors.initials: U
authors.lastname: Garbin
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D012907:Smoking / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; C099252:oxidized low density lipoprotein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase