Abstract 13647: Genetic Deletion of Interleukin-22 Prevents Angiotensin II-Induced Cardiac Diastolic Dysfunction in Mouse

Abstract

Introduction: Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, which promotes STAT3 activation in targets cells. Although it has been shown that persistent activation of STAT3 causes myocardial hypertrophy and fibrosis, little is known about the effect of IL-22 in the pathogenesis of cardiac diastolic dysfunction. Hypothesis: We hypothesized that IL-22 would be a factor that cardiac diastolic dysfunction. Methods and Results: We used angiotensin II (AngII) infusion mouse model, which has been reported to increase serum IL-22 levels, to cause cardiac diastolic dysfunction. We first investigated the effect of IL-22 deletion to cardiac function. Wild-type (WT) mice and IL-22 deficient (IL-22 KO) mice were compared cardiac function after 2 weeks AngII infusion. Echocardiographic analysis showed no decrease in systolic function as indicated by EF in both groups. However, In WT mice, E/e' was significantly increased compared to before AngII infusion. In contrast to WT mice, E/e' was not increased in IL-22KO mice by AngII infusion. These results suggested that AngII- induced cardiac diastolic dysfunction was prevented in IL-22KO mice. Next, we analyzed the effect of IL-22 deletion to histological changes. Compared to WT mice, ventricular weight to body weight ratio was significantly smaller in IL-22KO mice after 2 weeks AngII infusion. Echocardiographic analysis also showed that ventricular wall thickness was suppressed in IL-22KO mice. Sirius red staining revealed no difference in myocardial fibrosis between WT mice and IL-22KO mice after 2weeks AngII infusion. Conclusions: These results suggest that IL-22 plays an important role in the pathogenesis of AngII- induced cardiac diastolic dysfunction and cardiac hypertrophy.