Abstract 12856: Interleukin-33 and Soluble ST2 Are Expressed in Human Nonrheumatic Aortic Valve Stenosis
BACKGROUND The number of patients with nonrheumatic aortic valve stenosis (NR-AS) is increasing in recent years. Many studies demonstrated that the etiology of NR-AS is associated with a pathophysiology of atherosclerosis. Inflammations play an important role in the pathogenesis of not only atherosclerosis but also NR-AS. IL-33 is a recent identified cytokine of the IL-1 family, and has immunomodulatory functions. Soluble ST2 (sST2) is a secreted form IL-33 receptor which is secreted in response to inflammatory signals, and inhibits to bind of IL-33 to ST2L, as a decoy receptor of ST2L. IL-33 plays a protective role in the development of atherosclerosis through inhibition of inflammatory response to the accumulating lipid in the vessel wall. The role of IL-33 and ST2 in NR-AS has not been investigated. Therefore, we investigated the expression and cellular localization of IL-33 and sST2 in human NR-AS valve.
METHODS Aortic valve samples were collected from 67 patients undergoing valve replacement surgery (40 NR-AS and 27 aortic regurgitation (AR)). Patients with significant diseases such as autoimmune diseases, infections, cancer, or renal failure were excluded. We investigated IL-33 and sST2 expression in human aortic valves by Western blot and immunohistochemical analyses. RESULTS The clinical characteristics, such as age, sex, the prevalences of underlying disease, and medication, were not significant different between NR-AS and AR. IL-33 was expressed in aortic valves in patients with both of NR-AS and AR, and there was no significant difference in IL-33 expression levels between NR-AS and AR valves. On the other hands, sST2 expression was markedly up-regulated in NR-AS than in AR. Double-immunohistochemical analysis showed that the majority of IL-33 positive cells in NR-AS valves were stained with CD68 positive macrophages. Likewise, sST2 was expressed with macrophages in NR-AS valves.
CONCLUSIONS IL-33 and sST2 were expressed in human NR-AS valves. Increased sST2 may participate in the pathogenesis of aortic valve stenosis through the inhibition of IL-33. sST2 blockade may be a novel therapeutic target for the progression of NR-AS.
- © 2012 by American Heart Association, Inc.