Therapeutic Targeting of Interleukin-11 Up-Regulated Angiotensin II Induced Atrial Fibrosis in Mice

Abstract Purpose Inflammatory cytokines are closely associated with developing cardiac fibrosis. This research aimed to explore the significant role of IL-11 in atrial fibrosis progression and potential therapeutic targets. Methods 367 subjects were included in the case-control study. Blood samples were analyzed for the level of IL-11 by enzyme-linked immunosorbent assay (ELISA). Angiotensin II (Ang II) treated fibrosis mouse models were generated and expression of IL-11 mRNA and protein were detected by RT-qPCR and western blot. IL-11 antagonist was used to evaluate arterial fibrosis-related markers. Results The PeAF patients had significantly higher larger left atrial size (LAD), higher serum levels of hypertrophic protein BNP, proinflammatory cytokine high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) compared to PAF patients and healthy subjects (all P<0.05). Pearson correlation analysis revealed significant positive correlation between serum IL-11 and cardiac fibrosis markers BNP (r=0.394, P<0.001), CTX-I (r=0.418, P<0.001), PICP (r=0.306, P<0.001), PIIINP (r=0.335, P<0.001) and TGF-β1 (r=0.273, P<0.001). In the fibrosis mouse model, Ang II infusion significantly upregulated IL-11 mRNA and protein expression in the left atrium of mice (P<0.05) as well as staining intensity of Masson trichrome, the intensity of α-SMA, increased mRNA expression of collagen I and III in arterial tissue. An IL-11 antagonist, recombinant mouse IL-11 Rα Fc Chimera (rmIL-11Rα Fc), significantly attenuated Masson trichrome, number of α-SMA-positive myofibroblasts in atrial tissue. Also, significantly reduced the p-ERK1/2 in atrial tissue of mice infused with Ang II (P<0.05).Conclusion Our data speculated that IL-11 upregulated Ang ll induced atrial fibrosis. Therefore, IL-11 could be a potential therapeutic target for treating atrial.