Abstract 18514: Macrophage CARD9 Contributes to Cardiac Injury Following Myocardial Infarction by Regulating Inflammation and Apoptosis of Myocardiocytes

• Published in: Circulation (New York, N.Y.) Vol. 134; no. Suppl_1 Suppl 1; p. A18514
• Main Authors: Liu, Yan, Wang, Xuerui, Ma, Youcai, Zhang, Junmeng, Ren, Weihong, Du, Jie
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 11-11-2016
• ISSN: 0009-7322; 1524-4539

IntroductionWith high mortality rate, myocardial infarction (MI) is a severe type of coronary heart diseases. Innate immunity is activated after MI and mediates further injury to the heart. Caspase-associated recruitment domain 9 (CARD9) which is commonly expressed in macrophages elicits innate immunity.ObjectiveWe aim to investigate the role of CARD9 in pathogenesis of MI.Methods and ResultsMI was created by left coronary ligation in wild type (WT) and CARD9 knockout (KO) mice. The expression of CARD9 was increased robustly in the heart of WT mice as early as 1-day after infarction and declined on 7-day. Immunofluorescence staining and flow cytometry analysis showed that CARD9 expressed mostly in F4/80 positive macrophages. Mice with CARD9 KO showed improved left ventricular function and smaller infarct size on 28 days after infarction. CARD9 KO group demonstrated reduced macrophages recruitment, diminished plasma and cardiac expression levels of inflammatory cytokines, such as TNFα, IL-1β, IL-6, and MCP-1, and attenuated extracellular matrix degradation associated with a lower expression level of matrix metalloproteinase-9 compared with WT group. To explore the mechanism, we stimulated WT and CARD9 KO macrophages with necrotic myocardiocytes, and found that the induction of inflammatory cytokines secretion was depressed by CARD9 KO, which might result from blocking the activation of NF-κB. In vivo analysis confirmed the role of CARD9 KO on NF-κB activation after MI. Moreover, the secondary apoptosis of myocardiocytes was reduced by CARD9 knockout 3 days after MI, which might be attributed to inhibition of inflammation.ConclusionsMacrophage CARD9 mediated postinfarction necrotic cells induced inflammtion through NF-κB and subsequently aggravated the apoptosis of cardiac myocytes, leading to deteriorated left ventricular function and adverse remodeling.