Abstract 366: Inhibition of Interleukin-1ß by a Monoclonal Antibody Therapy Reduces Vascular Calcification in Ldlr-/- Mice
Objective: Given the link between cholesterol and activation of inflammation via interleukin-1β, we thus tested the effects of IL-1β inhibition on atherosclerotic calcification in mice.
Methods and Results: A mouse monoclonal antibody (mAB) against IL-1β or placebo was administered subcutaneously to Ldlr-/- and Tg(Pcsk9) models fed a Western diet. Drug level, anthropometric, lipid and glucose profiles were determined. PCSK9, SAA1 and cytokine expressions were measured by ELISA. Aortic calcification was determined by micro-CT and X-Ray densitometry and aortic flow velocity was assessed by ultrasound. Circulating levels of IL-1β in Ldlr-/- mice were significant twice that observed in Tg(Pcsk9) mice. Both mAb and placebo treated mice did not differ in their growth, lipid, glucose profiles and other cytokines while plasma SAA1 levels were lower in mAb-treated mice. Calcifications were significantly diminished in mAb-treatment Ldlr-/- mice (a reduction of 75% by X-ray and 96% by micro-CT) and reduced insignificantly in mAb-treatment Tg(Pcsk9) mice, whereas aortic flow velocity was unchanged in both models.
Conclusions: Herein we demonstrate that aortic calcifications can be inhibited by IL-1β mAb in LDL-receptor deficient mice. These results have a translational component to prevent vascular calcification in human and represent new evidence to rationalize targeting inflammation in cardiovascular disease.
Author Disclosures: Z. Awan: None. M. Denis: None. A. Roubtsova: None. H. Gram: Other Research Support; Modest; Scientist at Novartis. N.G. Seidah: None. J. Genest: None.
- © 2014 by American Heart Association, Inc.