Abstract 13025: Deficiency of Interleukin-1 Receptor Antagonist Promotes Angiotensin II-induced Aortic Inflammation and Aneurysm
Introduction: Angiotensin II (AngII) increases arterial pressure and induces inflammation. Although interleukin-1 receptor antagonist (IL-1Ra) is one of the most important anti-inflammatory cytokines, the role of IL-1Ra in AngII-induced aortic inflammation and aneurysm remains unknown.
Methods and Results: To determine the contrition of IL-1Ra to AngII-induced aortic inflammation, male wild-type (WT) (n=18) and IL-1Ra-deficient (IL-1Ra-/-) (n=18) mice were infused with AngII (3000ng/kg per minute) using subcutaneous osmotic pumps for 28 days. 7 days after infusion, real-time PCR of abdominal aorta in IL-1Ra-/- mice revealed significantly increased mRNA levels of IL-6 (2.1-fold, p<0.01), TNF-α (4.1-fold, p<0.01), and MMP-9 (20.3-fold, p<0.05) compared with WT mice. 14 days after infusion, both systolic blood pressure (178±21 vs 135±21 mmHg, p<0.01)and abdominal aortic width (1.02±0.12 vs 0.82±0.05 mm, p<0.01) in IL-1Ra-/- mice significantly increased compared with WT mice. Moreover, AngII infusion into IL-1Ra-/- mice also led to a significant increased occurrence of fatal aortic rupture (IL-1Ra-/-: 89% vs WT: 6%, p<0.01). Next, WT (n=6) and IL-1Ra-/- (n=6) mice were infuse with AngII for only 14 days, and histological analyses were performed at 28 days after operation. Interestingly, the abdominal aortic width in IL-1Ra-/- mice more significantly increased than those in WT mice (1.57±0.34 vs 0.80±0.04 mm, p<0.01), although IL-1Ra-/- and WT mice did not differ with regard to systolic blood pressure (105±15 vs 109±13 mmHg, p=0.61) at 28 days after operation. Histological analyses revealed there were numerous inflammatory cells around the abdominal aorta in IL-1Ra-/- mice, but not in WT mice. Furthermore, elastin staining showed destruction of the elastic lamina of abdominal aorta in IL-1Ra-/- mice. TNF-α protein expression also increased significantly in IL-1Ra-/- mice compared to WT mice at 28days.
Conclusions: The present study shows that IL-1Ra deficiency in mice led to increase inflammation and the development of aortic aneurysm after AngII infusion. Furthermore, our results also showed IL-1Ra deficiency continued the AngII-induced inflammation even though blood pressure was improved after cessation of AngII infusion.
Author Disclosures: K. Akita: None. K. Isoda: None. S. Isobe: None. T. Niida: None. H. Daida: None.
- © 2014 by American Heart Association, Inc.