RT Journal Article SR Electronic T1 aYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900424 DO 10.26508/lsa.201900424 VO 3 IS 1 A1 Chen, Jinmiao A1 Ma, Qing A1 King, Justin S A1 Sun, Yan A1 Xu, Bing A1 Zhang, Xiaoyu A1 Zohrabian, Sylvia A1 Guo, Haipeng A1 Cai, Wenqing A1 Li, Gavin A1 Bruno, Ivone A1 Cooke, John P A1 Wang, Chunsheng A1 Kontaridis, Maria A1 Wang, Da-Zhi A1 Luo, Hongbo A1 Pu, William T A1 Lin, Zhiqiang YR 2020 UL http://www.life-science-alliance.org/content/3/1/e201900424.abstract AB 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.