Abstract 18929: The Role of Clec9a in Atherosclerosis Development
Necrotic core formation during the development of atherosclerosis is associated with a chronic inflammatory response and promotes accelerated plaque development and instability. We hypothesized that sensing of necrotic cells by the C-type lectin receptors CLEC9A plays a determinant role in the inflammatory response of atherosclerosis. Reconstitution of lethally-irradiated Ldlr-/- with bone marrow from CLEC9A-/- mice significantly reduced atherosclerotic lesion size in aortic root (-45%, p=0,0059) after 5 weeks of FAT diet and (-40%, p=0,0017) after 7 weeks of FAT diet, as compared to mice transplanted with wild-type bone marrow-derived cells. However, no effect of CLEC9A was observed after 13 weeks of FAT diet (p=0,4996), suggesting early effect of CLEC9A on atherosclerosis development.The same phenotype was observed in 20-week-old Apoe-/-CLEC9A-/- compared to Apoe-/- mice put on chow diet (-50%, p=0,0022).Interestingly, an increase of IL-10 expression (+60%, p=0,0093) was observed in spleens of mice deficient for CLEC9A. Furthermore, the beneficial effect observed in CLEC9A-/- was abolished in CLEC9A-/-IL-10-/- compared to IL-10-/- (p=0,4452). Altogether, we showed that sensing of necrotic cores by CLEC9A promoted atherosclerosis development and this effect was mediated through a decrease of IL-10 production.
Author Disclosures: Y. Haddad: None. C. Lahoutte: None. M. Clément: None. L. Laurans: None. S. Metghalchi: None. X. Loyer: None. M. Vandestienne: None. J. Wain-Hobson: None. S. Potteaux: None. H. Ait-Oufella: None. B. Esposito: None. D. Sancho: None. A. Tedgui: None. Z. Mallat: None. S. Taleb: None.
- © 2016 by American Heart Association, Inc.