PMID- 34987647
OWN - NLM
STAT- MEDLINE
DCOM- 20220307
LR  - 20220307
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 12
IP  - 1
DP  - 2022
TI  - Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair.
PG  - 307-323
LID - 10.7150/thno.63642 [doi]
AB  - Background: Oxygen supplementation in myocardial infarction (MI) remains 
      controversial. Inflammation is widely believed to play a central role in 
      myocardial repair. A better understanding of these processes may lead to the 
      design of novel strategies complementary to MI treatment. Methods: To investigate 
      the role of hypoxia in inflammation and myocardial repair after acute MI, we 
      placed MI mice in a tolerable mild hypoxia (10% O(2)) chamber for 7 days and then 
      transferred the mice to ambient air for another 3 weeks. Results: We found that 
      the cumulative survival rate of the MI mice under hypoxia was significantly 
      higher than that under oxygen supplementation. Hypoxia promoted postinfarction 
      myocardial repair. Importantly, we found that hypoxia modulated the phenotypic 
      transition of blood monocytes from pro-inflammatory to pro-reparative in a timely 
      manner, leading to the subsequent discontinuation of inflammation in myocardial 
      tissues and promotion of myocardial repair post-MI. Specifically, cultured bone 
      marrow-derived macrophages (BMDMs) primed by hypoxia in vitro exhibited improved 
      reparative capacities and differed from M(1) and M(2) macrophages through the 
      AMPKalpha2 signaling pathway. The deletion of AMPKalpha2 in monocytes/macrophages 
      prevented the phenotypic transition induced by hypoxia and could not promote 
      myocardial repair after MI when transplanted into the myocardium. Conclusions: 
      Taken together, our work demonstrates that hypoxia promotes postinfarction 
      myocardial repair by modulating the blood monocyte/macrophage phenotypic 
      transition from pro-inflammatory to pro-reparative in a timely manner through the 
      AMPKalpha2 signaling pathway. Hypoxia priming might be an attractive translational 
      strategy for MI treatment by amplifying immune cells during early inflammation 
      and subsequent resolution and repair.
CI  - (c) The author(s).
FAU - Zhu, Yu
AU  - Zhu Y
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Yang, Wenjuan
AU  - Yang W
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Wang, Hailong
AU  - Wang H
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Tang, Fuqin
AU  - Tang F
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Zhu, Yun
AU  - Zhu Y
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Zhu, Qiong
AU  - Zhu Q
AD  - Department of Ultrasound, the Second Affiliated Hospital, Army Medical 
      University, 400037, Chongqing, China.
FAU - Ma, Ruiyan
AU  - Ma R
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Jian, Zhao
AU  - Jian Z
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
FAU - Xiao, Yingbin
AU  - Xiao Y
AD  - Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
AD  - Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army 
      Medical University, 400037, Chongqing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220101
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
SB  - IM
MH  - Animals
MH  - Hypoxia/*metabolism
MH  - Inflammation/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Infarction/*metabolism
MH  - *Myocardium/metabolism/pathology
MH  - Ventricular Remodeling
PMC - PMC8690923
OTO - NOTNLM
OT  - AMPKalpha2
OT  - hypoxia
OT  - monocytes/macrophages
OT  - myocardial infarction
OT  - phenotypic transition
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2022/01/07 06:00
MHDA- 2022/03/08 06:00
PMCR- 2022/01/01
CRDT- 2022/01/06 05:55
PHST- 2021/06/07 00:00 [received]
PHST- 2021/10/26 00:00 [accepted]
PHST- 2022/01/06 05:55 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/03/08 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - thnov12p0307 [pii]
AID - 10.7150/thno.63642 [doi]
PST - epublish
SO  - Theranostics. 2022 Jan 1;12(1):307-323. doi: 10.7150/thno.63642. eCollection 
      2022.