Extracellular ATP Induces Vascular Inflammation and Atherosclerosis via Purinergic Receptor Y 2 in Mice

• DOI: 10.1161/atvbaha.115.307397
• Publication Date: 2016-06-24T03:04:14Z
• Authors: Peter Stachon; Serjosha Geis; Alexander Peikert; Adrian Heidenreich; Nathaly Anto Michel; Fatih Ünal; Natalie Hoppe; Bianca Dufner; Lisa Schulte; Timoteo Marchini; Sanja Cicko; Korcan Ayata; Andreas Zech; Dennis Wolf; Ingo Hilgendorf; Florian Willecke; Jochen Reinöhl; Constantin von zu...; Christoph Bode; Marco Idzko; Andreas Zirlik
• Keywords: Purinergic Signalling

Objective— A solid body of evidence supports a role extracellular ATP and its P2 receptors in innate adaptive immunity. It promotes inflammation as danger signal various chronic inflammatory diseases. Thus, we hypothesize contribution receptor P2Y 2 vascular atherosclerosis. Approach Results— Extracellular induced leukocyte rolling, adhesion, migration vivo assessed by intravital microscopy sterile peritonitis. To test the atherosclerosis, or saline control was injected intraperitoneally 3× week low-density lipoprotein −/− mice consuming high cholesterol diet. Atherosclerosis significantly increased after 16 weeks ATP-treated (n=13; group, 0.26 mm2; 0.33 P =0.01). gain into ATP-receptor ATP-induced recruitment, administered systemically -deficient -competent mice. In mice, adhesion reduced microscopy. expression atherosclerosis measured real-time polymerase chain reaction immunohistochemistry demonstrates an mainly caused influx -expressing macrophages. investigate functional atherogenesis, consumed After weeks, showed atherosclerotic lesions with decreased macrophages compared (n=11; aortic arch: 0.25 mm ; -deficient, 0.14 =0.04). Mechanistically, from expressed less cell molecule-1 intercellular RNA. Conclusions— We show that induces via activation .