Abstract 579: Lack of Interleukin-19 Exacerbates Experimental Atherosclerosis
Interleukin-19 (IL-19) is a Th2 interleukin and a member of an IL-10 subfamily. Previous studies from our laboratory suggest an anti-inflammatory role for IL-19 outside the immune system, and for the vasculature in particular. Significantly more IL-19 is expressed in human atherosclerotic plaque from symptomatic rather than asymptomatic patients. However, addition of rIL-19 to LDLR-/- mice could significantly reduce atherosclerosis, suggesting that IL-19 expression is a compensatory, counter-regulatory mechanism. The purpose of this study was to test the hypothesis that absence of IL-19 results in increased atherosclerosis, and to characterize potential mechanisms for these effects. LDLR-/- mice were crossed with IL-19-/- mice, and homozygous double knock outs (DKO) were fed a high fat atherogenic diet for 14 weeks and compared with LDLR-/- mice. En face oil red O staining demonstrated that loss of IL-19 significantly exacerbated development of plaque in the aortic arch (13.41%+/-1.04 vs 21.13) +/-1.18, P<0.0001 for LDLR and DKO). Preliminary experiments were performed in which DKO were injected with 10ng/g/day rIL-19 or saline as control, and plaque quantitated en face staining. DKO mice rescued with rIL-19 had less plaque compared with saline controls (15.85+/-2.09% vs 22.43+/-2.80%, P=0.07). There was no significant difference in weight gain or serum cholesterol levels between these mice. As a first step to identify mechanisms, differences in cholesterol uptake in macrophage and VSMC were examined. Cholesterol uptake in BMDM from IL-19-/- mice were significantly decreased compared to wild-type controls (P<0.001). Conversely, cholesterol uptake in VSMC from IL-19-/- mice was significantly increased compared to wild-type (P<0.001). These data suggest that IL-19 plays an important part in development of atherosclerosis, with one potential mechanism being alterations in cholesterol homeostasis.
Author Disclosures: M. Ray: None. J. Richards: None. K. Gabunia: None. S. Kelemen: None. M. Autieri: None.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.