Details

Autor(en) / Beteiligte

• Yamamoto, Mai
• Yasukawa, Hideo
• Takahashi, Jinya
• Nohara, Shoichiro
• Sasaki, Tomoko
• Shimozono, Koutatsu
• Shibata, Tatsuhiro
• Yanai, Toshiyuki
• Mawatari, Kazutoshi
• Nagata, Takanobu
• Fukumoto, Yoshihiro

Titel

Abstract 13343: Lack of Interleukin-22 Increases Cardiac Rupture After Myocardial Infarction in Mice

Ist Teil von

• Circulation (New York, N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A13343-A13343

Ort / Verlag

by the American College of Cardiology Foundation and the American Heart Association, Inc

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• IntroductionInterleukin-22 (IL-22) is a member of the IL-10 cytokine family, which mainly targets epithelial cells, as opposed to immune cells. Although it has been shown that IL-22 activates STAT3 signaling pathway and plays a role in tissue protection, little is known about the role of IL-22 in the pathogenesis of cardiac remodeling after acute myocardial infarction (AMI).HypothesisWe hypothesized that IL-22 would play protective roles in cardiac remodeling after AMI.Methods and ResultsWe first evaluated that administration of recombinant IL-22 can activate STAT3 in the heart. Western blot analysis and immunostaining revealed that the significant rapid STAT3 activation in the myocardium after administration of recombinant IL-22 (p<0.01). Real-time PCR detected the expression of IL-22 and IL-22 receptor subunit alpha 1 (IL-22RA1) in the heart of wild type mice and those expressions were significantly increased 2 days after AMI (p<0.05). These results suggested that the IL-22 signaling pathway could be activated in the heart after AMI. To determine the effects of IL-22 to the cardiac remodeling, we induced AMI in the IL-22 deficient (IL-22 KO) mice. The IL-22 KO mice had significantly less survival rate than the wild type mice after AMI (p<0.01). Approximately 80% of the IL-22 KO mice died from cardiac rupture after AMI. Immunostaining revealed that phospho-STAT3 positive cells were less in the IL-22 KO mice than in the wild type mice at 3 days after AMI (p<0.05). The expressions of matrix metalloproteinase2 (MMP2), MMP9, IL-1β and IL-6 were comparable between wild type mice and IL-22 KO mice. On the other hand, MMP13 (also known as collagenase-3) and TNF-α expression in the hearts after AMI was significantly higher in IL-22 KO mice than that in wild type mice (p<0.05). We also found that myofibroblast marker α-smooth muscle actin (αSMA) positive cells were markedly higher in the hearts after AMI in IL-22 KO mice compared with wild type mice.ConclusionLack of IL-22 promotes cardiac rupture accompanied by the reduced activation of STAT3 and the increased expression of MMP13 and TNF-α. IL-22 may prevent cardiac rupture after AMI possibly through the activation of the STAT3 signaling pathway.