title: Differential Expression of Lipoprotein-Associated Phospholipase A2 in Monocyte Subsets: Impact of Uremia and Atherosclerosis.
abstract: BACKGROUND
  Monocytic products, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), may participate in the development of atherosclerosis. Heterogeneity of monocytes is widely acknowledged. Classical, intermediate, and non-classical subsets can be discerned. Recently, an inflammatory, pro-atherogenic monocyte population could be identified in hemodialysis patients. In this study, we investigated the expression of Lp-PLA2 on leucocytes and different monocyte subpopulations and their possible role in uremia, inflammation, and atherosclerosis.
  
  
  METHODS
  Chronic kidney disease stage 5-D (CKD5-D; n = 57), healthy control subjects with hs-C-reactive protein (CRP) levels ≤1 mg/L (CO-N, n = 22) and a control group with inflammatory activation (CRP levels >1 mg/L, CO-I, n = 29) were enrolled in this cross-sectional observation. The CKD5-D cohort was dichotomized into patients with (A+) and without subclinical atherosclerosis (A-) by carotid artery ultrasound measurement. Lp-PLA2 activity was determined in plasma samples, Lp-PLA2 mRNA expression analysis in leucocytes, and sorted monocyte subsets. Effects of Lp-PLA2 overexpression were studied in classical vs. intermediate and non-classical subsets.
  
  
  RESULTS
  The classical monocytes expressed the highest Lp-PLA2 mRNA levels as compared to other subpopulations. CKD5-D patients revealed significantly higher Lp-PLA2 transcripts, as well as higher Lp-PLA2 plasma activity as compared to healthy and "inflammatory" controls. In vitro data confirmed that uremia significantly contributes to Lp-PLA2 mRNA upregulation. Non-classical monocytes of A+ patients revealed significant higher Lp-PLA2 mRNA compared to A-.
  
  
  CONCLUSIONS
  Uremic environment but not inflammation per se increases plasma Lp-PLA2 activity and upregulates monocytic Lp-PLA2 mRNA expression. The highest Lp-PLA2 levels were found in the classical and not in the inflammatory subsets. Atherosclerosis also contributes to a subset-specific increase in Lp-PLA2 mRNA expression.
authors.affiliation: Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Ulrich
authors.forename: Bogusz
authors.initials: B
authors.lastname: Trojanowicz
authors.forename: Roman
authors.initials: R
authors.lastname: Fiedler
authors.forename: Felix
authors.initials: F
authors.lastname: Kohler
authors.forename: Anna-Franziska
authors.initials: AF
authors.lastname: Wolf
authors.forename: Eric
authors.initials: E
authors.lastname: Seibert
authors.forename: Matthias
authors.initials: M
authors.lastname: Girndt
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000235:genetics*; D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007962:Leukocytes / Q000201:enzymology; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000201:enzymology*; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015854:Up-Regulation; D014511:Uremia / Q000097:blood / Q000201:enzymology* / Q000235:genetics*
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human