AYAP modRNA reduces cardiac inflammation and hypertrophy in a murine ischemia-reperfusion model

Jinmiao Chen, Qing Ma, Justin S. King, Yan Sun, Bing Xu, Xiaoyu Zhang, Sylvia Zohrabian, Haipeng Guo, Wenqing Cai, Gavin Li, Ivone Bruno, John P. Cooke, Chunsheng Wang, Maria Kontaridis, Da Zhi Wang, Hongbo Luo, William T. Pu, Zhiqiang Lin

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere201900424
JournalLife Science Alliance
Volume3
Issue number1
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis

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