PMID- 37689005
OWN - NLM
STAT- Publisher
LR  - 20231011
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 183
DP  - 2023 Oct
TI  - Myeloid-specific deletion of Capns1 attenuates myocardial infarction injury via 
      restoring mitochondrial function and inhibiting inflammasome activation.
PG  - 54-66
LID - S0022-2828(23)00139-6 [pii]
LID - 10.1016/j.yjmcc.2023.08.006 [doi]
AB  - BACKGROUND: Mitochondrial dysfunction of macrophage-mediated inflammatory 
      response plays a key pathophysiological process in myocardial infarction (MI). 
      Calpains are a well-known family of calcium-dependent cysteine proteases that 
      regulate a variety of processes, including cell adhesion, proliferation, and 
      migration, as well as mitochondrial function and inflammation. CAPNS1, the common 
      regulatory subunit of calpain-1 and 2, is essential for the stabilization and 
      activity of the catalytic subunit. Emerging studies suggest that calpains may 
      serve as key mediators in mitochondria and NLRP3 inflammasome. This study 
      investigated the role of myeloid cell calpains in MI. METHODS: MI models were 
      constructed using myeloid-specific Capns1 knockout mice. Cardiac function, 
      cardiac fibrosis, and inflammatory infiltration were investigated. In vitro, bone 
      marrow-derived macrophages (BMDMs) were isolated from mice. Mitochondrial 
      function and NLRP3 activation were assessed in BMDMs under LPS stimulation. 
      ATP5A1 knockdown and Capns1 knock-out mice were subjected to MI to investigate 
      their roles in MI injury. RESULTS: Ablation of calpain activities by Capns1 
      deletion improved the cardiac function, reduced infarct size, and alleviated 
      cardiac fibrosis in mice subjected to MI. Mechanistically, Capns1 knockout 
      reduced the cleavage of ATP5A1 and restored the mitochondria function thus 
      inhibiting the inflammasome activation. ATP5A1 knockdown antagonized the 
      protective effect of Capns1 mKO and aggravated MI injury. CONCLUSION: This study 
      demonstrated that Capns1 depletion in macrophages mitigates MI injury via 
      maintaining mitochondrial homeostasis and inactivating the NLRP3 inflammasome 
      signaling pathway. This study may offer novel insights into MI injury treatment.
CI  - Copyright (c) 2023. Published by Elsevier Ltd.
FAU - Xiao, Zilong
AU  - Xiao Z
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
FAU - Wei, Xiang
AU  - Wei X
AD  - Department of Cardiology, Shanghai Fifth People's Hospital, Fudan University, 
      Shanghai, China.
FAU - Li, Minghui
AU  - Li M
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China.
FAU - Yang, Kun
AU  - Yang K
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China.
FAU - Chen, Ruizhen
AU  - Chen R
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China.
FAU - Su, Yangang
AU  - Su Y
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China.
FAU - Yu, Ziqing
AU  - Yu Z
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China.
FAU - Liang, Yixiu
AU  - Liang Y
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China. Electronic address: 
      liangyixiu@fudan.edu.cn.
FAU - Ge, Junbo
AU  - Ge J
AD  - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; 
      Shanghai Institute of Cardiovascular Diseases, Shanghai, China; National Clinical 
      Research Center for Interventional Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20230907
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
SB  - IM
OTO - NOTNLM
OT  - Calpains
OT  - Macrophages
OT  - Mitochondria
OT  - Myocardial infarction
OT  - NLRP3
COIS- Declaration of Competing Interest None.
EDAT- 2023/09/10 00:42
MHDA- 2023/09/10 00:42
CRDT- 2023/09/09 18:08
PHST- 2023/04/26 00:00 [received]
PHST- 2023/08/29 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/09/10 00:42 [pubmed]
PHST- 2023/09/10 00:42 [medline]
PHST- 2023/09/09 18:08 [entrez]
AID - S0022-2828(23)00139-6 [pii]
AID - 10.1016/j.yjmcc.2023.08.006 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2023 Oct;183:54-66. doi: 10.1016/j.yjmcc.2023.08.006. Epub 
      2023 Sep 7.