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 language | English (US) |
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Pages (from-to) | 2624-2633 |
Number of pages | 10 |
Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
Volume | 31 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2011 |
Externally published | Yes |
Keywords
- atherosclerosis
- chronic infection
- inflammation
- oxidative stress
- unfolded protein response
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine