@article{c75ad54f87d7420fa3c9b68e2fe34ea7,
title = "AYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model",
abstract = "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.",
author = "Jinmiao Chen and Qing Ma and King, {Justin S.} and Yan Sun and Bing Xu and Xiaoyu Zhang and Sylvia Zohrabian and Haipeng Guo and Wenqing Cai and Gavin Li and Ivone Bruno and Cooke, {John P.} and Chunsheng Wang and Maria Kontaridis and Wang, {Da Zhi} and Hongbo Luo and Pu, {William T.} and Zhiqiang Lin",
note = "Funding Information: We thank Alexander Von Gise from the University of Hannover for critically reviewing the manuscript. Sources of Funding: J Chen was supported by a Scholarship Fund from China Scholarship Council. Z Lin was supported by American Heart Association Scientist Development Grant 15SDG25590001, Progenitor Cell Biology Consortium ?JUMP START? AWARDS, 5U01HL099997-07, and National Institutes of Health HL138454-01. WT Pu was supported by National Institutes of Health R01 HL116461. Funding Information: We thank Alexander Von Gise from the University of Hannover for critically reviewing the manuscript. Sources of Funding: J Chen was supported by a Scholarship Fund from China Scholarship Council. Z Lin was supported by American Heart Association Scientist Development Grant 15SDG25590001, Progenitor Cell Biology Consortium “JUMP START” AWARDS, 5U01HL099997-07, and National Institutes of Health HL138454-01. WT Pu was supported by National Institutes of Health R01 HL116461. Publisher Copyright: {\textcopyright} 2019 Chen et al. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
doi = "10.26508/lsa.201900424",
language = "English (US)",
volume = "3",
journal = "Life Science Alliance",
issn = "2575-1077",
publisher = "Rockefeller University Press",
number = "1",
}