title: Evidence supporting a key role of Lp-PLA2-generated lysophosphatidylcholine in human atherosclerotic plaque inflammation.
abstract: OBJECTIVE
  To determine whether the level of lysophosphatidylcholine (lysoPC) generated by lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with severity of inflammation in human atherosclerotic plaques. Elevated plasma Lp-PLA2 is associated with increased cardiovascular risk. Lp-PLA2 inhibition reduces atherosclerosis. Lp-PLA2 hydrolyzes low-density lipoprotein-oxidized phospholipids generating lysoPCs. According to in vitro studies, lysoPCs are proinflammatory but the association between their generation and plaque inflammation remains unknown.
  
  
  RESULTS
  Inflammatory activity in carotid plaques (162 patients) was determined immunohistochemically and by analyzing cytokines in homogenates (multiplex immunoassay). LysoPCs were quantified using mass spectrometry and Lp-PLA2 and the lysoPC metabolite lysophosphatidic acid (LPA) by ELISA. There was a strong correlation among lysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 in plaques. LysoPC 16:0, 18:0, 18:1, LPA, and Lp-PLA2 correlated with interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-1β, regulated on activation normal T-cell expressed and secreted, and tumor necrosis factor-α in plaques. High lysoPC and Lp-PLA2 correlated with increased plaque macrophages and lipids and with low content of smooth muscle cells, whereas LPA only correlated with plaque macrophages. Lp-PLA2, lysoPC 16:0, 18:0, and 18:1, but not LPA were higher in symptomatic than in asymptomatic plaques.
  
  
  CONCLUSIONS
  The associations among Lp-PLA2, lysoPCs, LPA, and proinflammatory cytokines in human plaques suggest that lysoPCs play a key role in plaque inflammation and vulnerability. Our findings support Lp-PLA2 inhibition as a possible strategy for the prevention of cardiovascular disease.
authors.affiliation: Experimental Cardiovascular Research Group, Clinical Research Center, Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gonçalves
authors.forename: Andreas
authors.initials: A
authors.lastname: Edsfeldt
authors.forename: Na Young
authors.initials: NY
authors.lastname: Ko
authors.forename: Helena
authors.initials: H
authors.lastname: Grufman
authors.forename: Katarina
authors.initials: K
authors.lastname: Berg
authors.forename: Harry
authors.initials: H
authors.lastname: Björkbacka
authors.forename: Mihaela
authors.initials: M
authors.lastname: Nitulescu
authors.forename: Ana
authors.initials: A
authors.lastname: Persson
authors.forename: Marie
authors.initials: M
authors.lastname: Nilsson
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Jan
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000032:analysis*; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D016893:Carotid Stenosis / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000032:analysis* / Q000097:blood; D008244:Lysophosphatidylcholines / Q000032:analysis* / Q000097:blood; D008246:Lysophospholipids / Q000032:analysis; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000276:immunology; D054467:Phospholipases A2 / Q000032:analysis*; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human; C032881:lysophosphatidic acid