Abstract 16502: Defiency of Purinergic Receptor P2X7 Reduces Atherosclerosis in Mice
Introduction: As shown in different previous studies, extracellular nucleotides such as ATP or UDP play an important role in chronic inflammatory diseases like COPD, Asthma, and atherosclerosis. These extracellular nucleotides bind to purinergic receptors, e. g. P2X7, promoting a danger signal and lead to inflammatory cell recruitment.
Hypothesis: We hypothesized a role of the signal axis ATP - P2X7 in the chronic disease of atherosclerosis.
Methods: LDL-receptor deficient mice (LDLR -/-) or P2X7-defcient mice were fed for 16 weeks with High Cholesterol or chow Diet (HCD). P2X7 expression and atherosclerosis was assessed by qPCR and immunohistochemistry. Intravital microscopy was performed in P2X7 competent and deficient mice after stimulation with ATP. Leukocyte migration was assessed by Boyden Chamber Assay.
Results: We found significant more expression of P2X7 mostly in lesional macrophages in atherosclerotic vessels . In a next step, we crossed LDLR-/- mice with P2X7-/- mice. The P2X7-/- LDLR-/- mice were fed with HCD for 16 weeks. P2X7-competent LDLR-/- mice served as control group. P2X7-knockout mice contained smaller atherosclerotic lesions in the aortic arches than P2X7-competent mice (lesions mean P2X7-/- LDLR-/- = 0.084cm2, lesions mean LDLR-/- = 0.162cm2; n=20, p=0.004). To gain into the role of P2X7 in leukocyte recruitment, P2X7 competent or deficient mice were stimulated with 100nmol ATP. More leukocytes role and adhere on the vessel wall of P2X7 competent compared to P2X7 deficient mice as shown by intravital microscopy. Moreover the leukocyte migration in the Boyden Chamber Assay is reduced in P2RX7-/- LDLR-/- mice comparing to LDLR-/- mice after ATP-stimulation.
Conclusions: We could show that P2X7 is overexpressed in atherosclerosis. P2X7 deficiency leads to less plaque formation in the aortic arches. Mechanistically the leukocyte recruitment is decreased in P2X7 deficient mice after ATP-Stimulation.
Author Disclosures: P. Stachon: None. A. Heidenreich: None. J. Merz: None. N. Hoppe: None. C. Bode: None. M. Idzko: None. A. Zirlik: None.
- © 2016 by American Heart Association, Inc.