Theranostics 2022; 12(1):307-323. doi:10.7150/thno.63642 This issue Cite

Research Paper

Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair

Yu Zhu1,2, Wenjuan Yang1,2, Hailong Wang1, Fuqin Tang1,2, Yun Zhu1,2, Qiong Zhu3, Ruiyan Ma1,2, Zhao Jian1,2✉, Yingbin Xiao1,2✉

1. Department of Cardiovascular Surgery, the Second Affiliated Hospital, Army Medical University, 400037, Chongqing, China.
2. Vascular Injury and Repair Laboratory, the Second Affiliated Hospital, Army Medical University, 400037, Chongqing, China.
3. Department of Ultrasound, the Second Affiliated Hospital, Army Medical University, 400037, Chongqing, China.

Citation:
Zhu Y, Yang W, Wang H, Tang F, Zhu Y, Zhu Q, Ma R, Jian Z, Xiao Y. Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair. Theranostics 2022; 12(1):307-323. doi:10.7150/thno.63642. https://www.thno.org/v12p0307.htm
Other styles

File import instruction

Abstract

Graphic abstract

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% O2) 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 M1 and M2 macrophages through the AMPKα2 signaling pathway. The deletion of AMPKα2 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 AMPKα2 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.

Keywords: hypoxia, myocardial infarction, monocytes/macrophages, phenotypic transition, AMPKα2


Citation styles

APA
Zhu, Y., Yang, W., Wang, H., Tang, F., Zhu, Y., Zhu, Q., Ma, R., Jian, Z., Xiao, Y. (2022). Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair. Theranostics, 12(1), 307-323. https://doi.org/10.7150/thno.63642.

ACS
Zhu, Y.; Yang, W.; Wang, H.; Tang, F.; Zhu, Y.; Zhu, Q.; Ma, R.; Jian, Z.; Xiao, Y. Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair. Theranostics 2022, 12 (1), 307-323. DOI: 10.7150/thno.63642.

NLM
Zhu Y, Yang W, Wang H, Tang F, Zhu Y, Zhu Q, Ma R, Jian Z, Xiao Y. Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair. Theranostics 2022; 12(1):307-323. doi:10.7150/thno.63642. https://www.thno.org/v12p0307.htm

CSE
Zhu Y, Yang W, Wang H, Tang F, Zhu Y, Zhu Q, Ma R, Jian Z, Xiao Y. 2022. Hypoxia-primed monocytes/macrophages enhance postinfarction myocardial repair. Theranostics. 12(1):307-323.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image