title: Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule.
abstract: OBJECTIVE
  Chronic infection has long been postulated as a stimulus for atherogenesis. Pseudomonas aeruginosa infection has been associated with increased atherosclerosis in rats, and these bacteria produce a quorum-sensing molecule 3-oxo-dodecynoyl-homoserine lactone (3OC12-HSL) that is critical for colonization and virulence. Paraoxonase 2 (PON2) hydrolyzes 3OC12-HSL and also protects against the effects of oxidized phospholipids thought to contribute to atherosclerosis. We now report the response of human aortic endothelial cells (HAECs) to 3OC12-HSL and oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (Ox-PAPC) in relation to PON2 expression.
  
  
  RESULTS
  Using expression profiling and network modeling, we identified the unfolded protein response (UPR), cell cycle genes, and the mitogen-activated protein kinase signaling pathway to be heavily involved in the HAEC response to 3OC12-HSL. The network also showed striking similarities to a network created based on HAEC response to Ox-PAPC, a major component of minimally modified low-density lipoprotein. HAECs in which PON2 was silenced by small interfering RNA showed increased proinflammatory response and UPR when treated with 3OC12-HSL or Ox-PAPC.
  
  
  CONCLUSIONS
  3OC12-HSL and Ox-PAPC influence similar inflammatory and UPR pathways. Quorum sensing molecules, such as 3OC12-HSL, contribute to the proatherogenic effects of chronic infection. The antiatherogenic effects of PON2 include destruction of quorum sensing molecules.
authors.affiliation: Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA, USA.
authors.forename: Juyong Brian
authors.initials: JB
authors.lastname: Kim
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Xia
authors.forename: Casey E
authors.initials: CE
authors.lastname: Romanoski
authors.forename: Sangderk
authors.initials: S
authors.lastname: Lee
authors.forename: YongHong
authors.initials: Y
authors.lastname: Meng
authors.forename: Yi-Shou
authors.initials: YS
authors.lastname: Shi
authors.forename: Noam
authors.initials: N
authors.lastname: Bourquard
authors.forename: Ke Wei
authors.initials: KW
authors.lastname: Gong
authors.forename: Zachary
authors.initials: Z
authors.lastname: Port
authors.forename: Victor
authors.initials: V
authors.lastname: Grijalva
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Judith A
authors.initials: JA
authors.lastname: Berliner
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Diana M
authors.initials: DM
authors.lastname: Shih
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006714:Homoserine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000494:pharmacology*; D053038:Quorum Sensing; D034741:RNA, Small Interfering / Q000494:pharmacology; D013312:Stress, Physiological / Q000187:drug effects* / Q000502:physiology
chemical_list: D008077:Lipoproteins, LDL; C109860:N-(3-oxododecanoyl)homoserine lactone; D010743:Phospholipids; D034741:RNA, Small Interfering; D006714:Homoserine; D043303:Aryldialkylphosphatase; D015107:4-Butyrolactone