Abstract 12302: Interleukin-22 Deficiency Exacerbates Right Ventricular Remodeling and Tricuspid Regurgitation During Pressure Overload

Introduction: Right ventricle (RV) remodeling is associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in left ventricular remodeling after acute myocardial infarction; however, the role of IL-22 in the development of RV remodeling remains elusive. Hypothesis: IL-22 would inhibit the development of RV remodeling during pressure overload. Methods: Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band> 25 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Four weeks after PAB, RV function was measured by echocardiography, and 2 weeks after PAB, real-time PCR analysis was performed to measure IL-22 receptor subunit alpha 1 (IL-22RA1), and endogenous IL-22 inhibitor IL-22 binding protein (IL-22BP). Results: Four weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/BW: 1.4±0.2% vs 1.7±0.2%, P=0.047). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 4 weeks safter PAB. Compared with wild type mice, IL-22 KO mice had reduced TAPSE (0.64±0.11mm vs. 0.47±0.06mm, P=0.002) and FAC (30.6±6.6% vs. 23.5±4.4%, P=0.019), whereas RVEDV was increased (12.8±2.2mm 2 vs. 17.1±2.5mm 2 , P=0.019). Four weeks after PAB, the frequency of tricuspid regurgitation (TR) in IL-22 KO mice was significantly higher than that in wild type mice (100% vs 30%, P=0.004). The expression of IL-22, IL-22RA1 and IL-22BP in the RV tended to increase 2 weeks after PAB (wild-type mice with PAB (n=3) vs. wild-type mice with sham; IL-22RA1: 1.489 vs 1.773, P=0.175, IL-22BP: 0.025 vs 0.067, p=0.005). Conclusions: These results suggest that IL-22 may play a preventive role in the development of RV remodeling and TR during pressure overload.