Paraoxonase-2 modulates stress response of endothelial cells to oxidized phospholipids and a bacterial quorum-sensing molecule

Juyong Brian Kim, Yu Rong Xia, Casey E. Romanoski, Sangderk Lee, Yonghong Meng, Yi Shou Shi, Noam Bourquard, Ke Wei Gong, Zachary Port, Victor Grijalva, Srinivasa T. Reddy, Judith A. Berliner, Aldons J. Lusis, Diana M. Shih

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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. Methods and 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. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)2624-2633
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number11
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • atherosclerosis
  • chronic infection
  • inflammation
  • oxidative stress
  • unfolded protein response

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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