PMID- 32321866
OWN - NLM
STAT- MEDLINE
DCOM- 20210623
LR  - 20221205
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 12
IP  - 540
DP  - 2020 Apr 22
TI  - Blocking the death checkpoint protein TRAIL improves cardiac function after 
      myocardial infarction in monkeys, pigs, and rats.
LID - 10.1126/scitranslmed.aaw3172 [doi]
LID - eaaw3172
AB  - Myocardial infarction (MI) is a leading cause of death worldwide for which there 
      is no cure. Although cardiac cell death is a well-recognized pathological 
      mechanism of MI, therapeutic blockade of cell death to treat MI is not 
      straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis 
      factor (TNF)-related apoptosis-inducing ligand] are up-regulated in MI, but their 
      roles in pathological remodeling are unknown. Here, we report that blocking TRAIL 
      with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing 
      cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, 
      TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, 
      directly and indirectly causing cardiac injury. Transcriptome profiling revealed 
      increased expression of inflammatory cytokines in infarcted heart tissue, which 
      was markedly reduced by TRAIL blockade. Together, our findings indicate that 
      TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by 
      affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic 
      strategy for treating MI.
CI  - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Wang, Yaohui
AU  - Wang Y
AUID- ORCID: 0000-0003-0165-6573
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Hailong
AU  - Zhang H
AUID- ORCID: 0000-0002-5392-9257
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Zhizeng
AU  - Wang Z
AUID- ORCID: 0000-0003-4847-948X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wei, Yinxiang
AU  - Wei Y
AUID- ORCID: 0000-0002-1699-1115
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Mingli
AU  - Wang M
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Liu, Meichen
AU  - Liu M
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Xuance
AU  - Wang X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
AD  - Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.
FAU - Jiang, Yinan
AU  - Jiang Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Shi, Gongning
AU  - Shi G
AD  - Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.
FAU - Zhao, Dongmei
AU  - Zhao D
AD  - Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.
FAU - Yang, Zhengyan
AU  - Yang Z
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Ren, Zhiguang
AU  - Ren Z
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Li, Jing
AU  - Li J
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Zhenkai
AU  - Zhang Z
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Zhenfeng
AU  - Wang Z
AUID- ORCID: 0000-0002-7407-7065
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Bei
AU  - Zhang B
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zong, Beibei
AU  - Zong B
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Lou, Xueke
AU  - Lou X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Liu, Chengguo
AU  - Liu C
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Zihui
AU  - Wang Z
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Hao
AU  - Zhang H
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Tao, Ningya
AU  - Tao N
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Li, Xuefang
AU  - Li X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Xingkun
AU  - Zhang X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Guo, Yafei
AU  - Guo Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Ye, Yang
AU  - Ye Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Qi, Yu
AU  - Qi Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Li, Hui
AU  - Li H
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Wang, Man
AU  - Wang M
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Guo, Rongxin
AU  - Guo R
AD  - Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.
FAU - Cheng, Guanchang
AU  - Cheng G
AD  - Henan University affiliated Huaihe Hospital, Kaifeng 475004, P.R. China.
FAU - Li, Shulian
AU  - Li S
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Liu, Guangchao
AU  - Liu G
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Chai, Lihui
AU  - Chai L
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Lou, Qiang
AU  - Lou Q
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Li, Xia
AU  - Li X
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Cui, Xiukun
AU  - Cui X
AUID- ORCID: 0000-0003-2555-3413
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Gao, Erhe
AU  - Gao E
AD  - Center for Translational Medicine, Temple University School of Medicine, 
      Philadelphia, PA 19140, USA.
FAU - Dong, Zheng
AU  - Dong Z
AD  - Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta 
      University and Charlie Norwood VA Medical Center, Augusta, GA 30912, USA.
FAU - Hu, Yanzhong
AU  - Hu Y
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China.
FAU - Chen, Youhai H
AU  - Chen YH
AUID- ORCID: 0000-0002-9695-6757
AD  - Department of Pathology and Laboratory Medicine, Perelman School of Medicine, 
      University of Pennsylvania, Philadelphia, PA 19104, USA. mayf@henu.edu.cn 
      yhc@pennmedicine.upenn.edu.
FAU - Ma, Yuanfang
AU  - Ma Y
AUID- ORCID: 0000-0001-5635-2660
AD  - Joint National Laboratory for Antibody Drug Engineering, Key Laboratory of Cell 
      and Molecular Immunology, School of Medical Sciences, Henan University, Kaifeng 
      475004, P.R. China. mayf@henu.edu.cn yhc@pennmedicine.upenn.edu.
LA  - eng
GR  - T32 DK007780/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Haplorhini
MH  - *Myocardial Infarction/drug therapy
MH  - Rats
MH  - *Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Swine
MH  - TNF-Related Apoptosis-Inducing Ligand
PMC - PMC9719290
MID - NIHMS1790396
COIS- Competing interests: Y.M., Y. Wang, Mingli Wang, J.Z., G.L., S.L., and Y.H. hold 
      a patent titled "Application of human sDR5 and sDR5-Fc as AMI therapeutic 
      candidate" (ZL 2012104426856, China). Y.M., Y. Wang, Hailong Zhang, Mingli Wang, 
      J.Z., G.L., S.L., and Y.H. hold a patent titled "sDR5-Fc fusion protein mutant 
      and use thereof" (ZL201510510981.9, China). Y.M., Y. Wang, Hailong Zhang, Mingli 
      Wang, J.Z., G.L., S.L., and Y.H. are inventors on patent application "sDR5-Fc 
      fusion protein mutant and use thereof" (PCT/CN2016/081552, USA). Y.H.C. is a 
      member of the advisory boards of Amshenn Inc. and Binde Inc. All other authors 
      declare that they have no competing interests.
EDAT- 2020/04/24 06:00
MHDA- 2021/06/24 06:00
PMCR- 2022/12/03
CRDT- 2020/04/24 06:00
PHST- 2018/12/08 00:00 [received]
PHST- 2019/06/26 00:00 [revised]
PHST- 2020/03/11 00:00 [accepted]
PHST- 2020/04/24 06:00 [entrez]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2021/06/24 06:00 [medline]
PHST- 2022/12/03 00:00 [pmc-release]
AID - 12/540/eaaw3172 [pii]
AID - 10.1126/scitranslmed.aaw3172 [doi]
PST - ppublish
SO  - Sci Transl Med. 2020 Apr 22;12(540):eaaw3172. doi: 10.1126/scitranslmed.aaw3172.