PMID- 37810172
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231031
IS  - 2573-9832 (Electronic)
IS  - 2573-9832 (Linking)
VI  - 5
IP  - 10
DP  - 2023 Oct
TI  - Progranulin deficiency exacerbates cardiac remodeling after myocardial 
      infarction.
PG  - 395-411
LID - 10.1096/fba.2023-00084 [doi]
AB  - Myocardial infarction (MI) is a lethal disease that causes irreversible 
      cardiomyocyte death and subsequent cardiovascular remodeling. We have previously 
      shown that the administration of recombinant progranulin (PGRN) protects against 
      myocardial ischemia and reperfusion injury. However, the post-MI role of PGRN 
      remains unclear. In the present study, we investigated the effects of PGRN 
      deficiency on cardiac remodeling after MI. Wild-type and PGRN-knockout mice were 
      subjected to MI by ligation of the left coronary artery for histological, 
      electrophysiological, and protein expression analysis. Cardiac macrophage 
      subpopulations were analyzed by flow cytometry. Bone marrow-derived macrophages 
      (BMDMs) were acquired and treated with LPS + IFN-gamma and IL-4 to evaluate mRNA 
      levels and phagocytic ability. PGRN expression was gradually increased in the 
      whole heart at 1, 3, and 7 days after MI. Macrophages abundantly expressed PGRN 
      at the border areas at 3 days post-MI. PGRN-knockout mice showed higher 
      mortality, increased LV fibrosis, and severe arrhythmia following MI. PGRN 
      deficiency increased the levels of CD206 and MerTK expression and macrophage 
      infiltration in the infarcted myocardium, which was attributed to a larger 
      subpopulation of cardiac CCR2(+) Ly6C(low) CD11b(+) macrophages. PGRN-deficient 
      BMDMs exhibited higher TGF-beta, IL-4R, and lower IL-1beta, IL-10 and increased acute 
      phagocytosis following stimulation of LPS and IFN-gamma. PGRN deficiency reduced 
      survival and increased cardiac fibrosis following MI with the induction of 
      abnormal subpopulation of cardiac macrophages early after MI, thereby providing 
      insight into the relationship between properly initiating cardiac repair and 
      macrophage polarization after MI.
CI  - (c) 2023 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on 
      behalf of The Federation of American Societies for Experimental Biology.
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.
AD  - Laboratory of Collaborative Research for Innovative Drug Discovery Gifu 
      Pharmaceutical University Gifu Japan.
FAU - Hara, Hideaki
AU  - Hara H
AD  - Molecular Pharmacology, Department of Biofunctional Evaluation Gifu 
      Pharmaceutical University Gifu Japan.
AD  - Laboratory of Collaborative Research for Innovative Drug Discovery Gifu 
      Pharmaceutical University Gifu Japan.
LA  - eng
PT  - Journal Article
DEP - 20230920
PL  - United States
TA  - FASEB Bioadv
JT  - FASEB bioAdvances
JID - 101733210
PMC - PMC10551273
OTO - NOTNLM
OT  - macrophage
OT  - myocardial infarction
OT  - progranulin
EDAT- 2023/10/09 06:41
MHDA- 2023/10/09 06:42
PMCR- 2023/09/20
CRDT- 2023/10/09 05:59
PHST- 2023/08/18 00:00 [received]
PHST- 2023/09/04 00:00 [revised]
PHST- 2023/08/22 00:00 [accepted]
PHST- 2023/10/09 06:42 [medline]
PHST- 2023/10/09 06:41 [pubmed]
PHST- 2023/10/09 05:59 [entrez]
PHST- 2023/09/20 00:00 [pmc-release]
AID - FBA21409 [pii]
AID - 10.1096/fba.2023-00084 [doi]
PST - epublish
SO  - FASEB Bioadv. 2023 Sep 20;5(10):395-411. doi: 10.1096/fba.2023-00084. eCollection 
      2023 Oct.