Abstract 153: IL-10 Accelerates Re-Endothelialization and Inhibits Post-injury Intimal Hyperplasia following Carotid Artery Denudation by Attenuating TNF-alpha-induced Endothelial Cell Dysfunction
The association of inflammation with atherosclerosis and restenosis is now fairly well established. Restenosis, a persistent complication of percutaneous vascular interventions, is thought to be a complex response to injury, which includes early thrombus formation, neointimal growth and acute inflammation. Mononuclear phagocytes are likely participants in the host response to vascular injury, via the secretion of cytokines and chemokines, including TNF-alpha (TNF). Others and we have previously shown that IL-10 inhibits TNF and other inflammatory mediators produced in response to cardiovascular injuries. The specific effect of IL-10 on endothelial cell (EC) biology is not well elucidated. Here we report that in a mouse model of carotid denudation, IL-10 knock-out mice (IL10KO) displayed significantly delayed ReEndothelialization and enhanced neointimal growth compared to their WT counterparts. Exogenous treatment of recombinant IL-10 dramatically blunted the inflammatory cell infiltration and neointimal thickening while significantly accelerating the recovery of the injured endothelium both WT and IL10KO mice. In vitro, IL10 co-treatment reversed TNF-mediated growth arrest, EC cell cycle inhibition, EC-monocyte adhesion and EC apoptosis. At signaling level, IL-10 reduced TNF-induced activation of JNK MAP kinase while simultaneously activating PI3K/Akt pathway. Because IL-10 function and signaling are important components for control of inflammatory responses, these results may provide insights necessary to develop strategies for modulating vascular repair and other accelerated arteriopathies, including transplant vasculopathy and vein graft hyperplasia.
Author Disclosures: S.K. Verma: None P. Krishnamurthy: None A.R. Mackie: None E.E. Vaughan: None M. Khan: None G.V. Srikanth: None V. Ramirez: None T. Abramova: None S. Misener: None G. Qin: None R. Kishore: None.
- © 2014 by American Heart Association, Inc.