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.