PMID- 38039836
OWN - NLM
STAT- MEDLINE
DCOM- 20240103
LR  - 20240106
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 691
DP  - 2024 Jan 8
TI  - Progranulin-deficient macrophages cause cardiotoxicity under hypoxic conditions.
PG  - 149341
LID - S0006-291X(23)01435-3 [pii]
LID - 10.1016/j.bbrc.2023.149341 [doi]
AB  - Myocardial infarction (MI) induces structural and electrical cardiac remodeling 
      in response to ischemic insult, causing lethal arrhythmias and sudden death. 
      Progranulin (PGRN) is a glycoprotein mainly expressed in macrophages that 
      modulates the immune responses. In this study, we investigated the direct 
      influence of PGRN knockout (Grn(-/-)) macrophages on post-MI pathophysiology. An 
      MI mouse model was established by ligating the left coronary artery for RNA 
      sequencing and electrocardiographic analysis. Bone marrow-derived macrophages 
      (BMDMs) were injected into mice and supernatant was collected for the measurement 
      of reactive oxygen species (ROS) levels and extracellular flux analysis. 
      Administration of Grn(-/-) BMDMs prolonged the QT intervals in the MI mouse 
      model. Moreover, genes highly expressed in macrophages were upregulated in 
      Grn(-/-) heart after MI. Post-hypoxic supernatant of Grn(-/-) BMDMs increased the 
      oxygen-glucose deprivation-induced cardiomyocyte death. Grn(-/-) BMDMs exhibited 
      increased ROS production, oxygen consumption, and extracellular acidification 
      under hypoxia and inflammatory conditions. These findings suggest that PGRN 
      deficiency causes cardiotoxicity via secretory components of macrophages that 
      exhibit metabolic abnormalities under hypoxia.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Sasaki, Takahiro
AU  - Sasaki T
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Kuse, Yoshiki
AU  - Kuse Y
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Nakamura, Shinsuke
AU  - Nakamura S
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan.
FAU - Shimazawa, Masamitsu
AU  - Shimazawa M
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu 
      Pharmaceutical University, Gifu, Japan. Electronic address: 
      shimazawa@gifu-pu.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20231128
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Progranulins)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Progranulins/metabolism
MH  - *Cardiotoxicity/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Macrophages/metabolism
MH  - *Myocardial Infarction/metabolism
MH  - Myocytes, Cardiac/metabolism
MH  - Disease Models, Animal
MH  - Hypoxia/genetics/metabolism
OTO - NOTNLM
OT  - Arrhythmia
OT  - Macrophage
OT  - Myocardial infarction
OT  - Progranulin
COIS- Declaration of competing interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Takahiro Sasaki reports financial support was provided by Japan 
      Society for the Promotion of Science; KAKENHI. If there are other authors, they 
      declare that they have no known competing financial interests or personal 
      relationships that could have appeared to influence the work reported in this 
      paper.
EDAT- 2023/12/02 00:42
MHDA- 2024/01/03 09:42
CRDT- 2023/12/01 18:12
PHST- 2023/11/23 00:00 [received]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2024/01/03 09:42 [medline]
PHST- 2023/12/02 00:42 [pubmed]
PHST- 2023/12/01 18:12 [entrez]
AID - S0006-291X(23)01435-3 [pii]
AID - 10.1016/j.bbrc.2023.149341 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2024 Jan 8;691:149341. doi: 
      10.1016/j.bbrc.2023.149341. Epub 2023 Nov 28.