TY - JOUR T1 - aYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900424 VL - 3 IS - 1 SP - e201900424 AU - Jinmiao Chen AU - Qing Ma AU - Justin S King AU - Yan Sun AU - Bing Xu AU - Xiaoyu Zhang AU - Sylvia Zohrabian AU - Haipeng Guo AU - Wenqing Cai AU - Gavin Li AU - Ivone Bruno AU - John P Cooke AU - Chunsheng Wang AU - Maria Kontaridis AU - Da-Zhi Wang AU - Hongbo Luo AU - William T Pu AU - Zhiqiang Lin Y1 - 2020/01/01 UR - https://www.life-science-alliance.org/content/3/1/e201900424.abstract N2 - Myocardial recovery from ischemia-reperfusion (IR) is shaped by the interaction of many signaling pathways and tissue repair processes, including the innate immune response. We and others previously showed that sustained expression of the transcriptional co-activator yes-associated protein (YAP) improves survival and myocardial outcome after myocardial infarction. Here, we asked whether transient YAP expression would improve myocardial outcome after IR injury. After IR, we transiently activated YAP in the myocardium with modified mRNA encoding a constitutively active form of YAP (aYAP modRNA). Histological studies 2 d after IR showed that aYAP modRNA reduced cardiomyocyte (CM) necrosis and neutrophil infiltration. 4 wk after IR, aYAP modRNA–treated mice had better heart function as well as reduced scar size and hypertrophic remodeling. In cultured neonatal and adult CMs, YAP attenuated H2O2- or LPS-induced CM necrosis. TLR signaling pathway components important for innate immune responses were suppressed by YAP/TEAD1. In summary, our findings demonstrate that aYAP modRNA treatment reduces CM necrosis, cardiac inflammation, and hypertrophic remodeling after IR stress. ER -