Abstract 146: Administration of Interleukin-19 Halts Progression of Pre-formed Plaque, Polarizes Macrophage, and Increases Macrophage Lipid Uptake.
Increased uptake of oxLDL by macrophage is proposed to be an atheroprotective mechanism to reduce plaque formation. It has been proposed that macrophage phenotype may be causative or at least associated with plaque severity. Several macrophage phenotypes have been classified, and M2 macrophage are considered to be anti-inflammatory and reparative. Interleukin-19 is a purported anti-inflammatory, Th2 interleukin, and we previously found that addition of rIL-19 could significantly reduce atherosclerosis in susceptible mice. The purpose of this study was to test the hypothesis that administration of exogenous IL-19 could attenuate progression of pre-formed atherosclerotic plaque, and to identify potential molecular mechanisms. LDLR-/- mice were fed high-fat diet for 12 weeks, then administered rIL-19 (10ng/g/day) or PBS for an additional 8 weeks while still consuming HFD. En face analysis demonstrated that IL-19 could halt, but not reverse existing plaque. M2 macrophage marker expression was significantly increased in aorta and spleen from IL-19 treated mice, in IL-19-treated bone marrow derived macrophage (BMDM) and primary human macrophage. IL-19 significantly decreased expression of inflammatory cytokines TNFa, IL-12p40, MCP-1 and IL-1b mRNA in BMDM. Addition of IL-19 to BMDM significantly increased oxLDL uptake as well as expression of lipid uptake receptors CD36, SRA-1, and SRB-1 in primary human macrophage. IL-19 increased expression and activation of PPARg. Knock down of PPARg significantly decreased IL-19 mediated expression of both lipid uptake receptors and uptake of oxLDL. Collectively, these data show that IL-19 can halt progression of established plaque by at least two mechanisms; M2 macrophage polarization, and increasing expression of lipid scavenger receptors and cholesterol uptake in a PPARg-dependent mechanism, suggesting therapeutic potential for this interleukin.
Author Disclosures: K. Gabunia: None. S. Ellison: None. S. Kelemen: None. F. Kako: None. W. Cornwell: None. P. Datta: None. T.J. Rogers: None. M.V. Autieri: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.