Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice

Background. After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium l...

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Main Authors: Jialiang Zhang, Fangyang Huang, Li Chen, Guoyong Li, Wenhua Lei, Jiahao Zhao, Yanbiao Liao, Yijian Li, Changming Li, Mao Chen
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Cardiovascular Therapeutics
Online Access:http://dx.doi.org/10.1155/2021/5530541
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author Jialiang Zhang
Fangyang Huang
Li Chen
Guoyong Li
Wenhua Lei
Jiahao Zhao
Yanbiao Liao
Yijian Li
Changming Li
Mao Chen
author_facet Jialiang Zhang
Fangyang Huang
Li Chen
Guoyong Li
Wenhua Lei
Jiahao Zhao
Yanbiao Liao
Yijian Li
Changming Li
Mao Chen
author_sort Jialiang Zhang
collection DOAJ
description Background. After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. Methods. MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. Results. Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-β, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. Conclusion. Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.
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issn 1755-5914
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publishDate 2021-01-01
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series Cardiovascular Therapeutics
spelling doaj-art-95aeeea814b243f1980b81839e537aad2025-02-03T06:12:04ZengWileyCardiovascular Therapeutics1755-59141755-59222021-01-01202110.1155/2021/55305415530541Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in MiceJialiang Zhang0Fangyang Huang1Li Chen2Guoyong Li3Wenhua Lei4Jiahao Zhao5Yanbiao Liao6Yijian Li7Changming Li8Mao Chen9Department of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Cardiology, West China Hospital, Sichuan University, Chengdu, ChinaBackground. After myocardial infarction, anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. Several studies have shown that lactate may serve as a modifier that influences phenotype of macrophage. However, the therapeutic role of sodium lactate in myocardial infarction (MI) is unclear. Methods. MI was established by permanent ligation of the left anterior descending coronary artery followed by injection of saline or sodium lactate. Cardiac function was assessed by echocardiography. The cardiac fibrosis area was assessed by Masson trichrome staining. Macrophage phenotype was detected via qPCR, flow cytometry, and immunofluorescence. Signaling proteins were measured by Western blotting. Results. Sodium lactate treatment following MI improved cardiac performance, enhanced anti-inflammatory macrophage proportion, reduced cardiac myocytes apoptosis, and increased neovascularization. Flow-cytometric analysis results reported that sodium lactate repressed the number of the IL-6+, IL-12+, and TNF-α+ macrophages among LPS-stimulated bone marrow-derived macrophages (BMDMs) and increased the mRNA levels of Arg-1, YM1, TGF-β, and IL-10. Mechanistic studies revealed that sodium lactate enhanced the expression of P-STAT3. Furthermore, a STAT3 inhibitor eliminated sodium lactate-mediated promotion macrophage polarization. Conclusion. Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3.http://dx.doi.org/10.1155/2021/5530541
spellingShingle Jialiang Zhang
Fangyang Huang
Li Chen
Guoyong Li
Wenhua Lei
Jiahao Zhao
Yanbiao Liao
Yijian Li
Changming Li
Mao Chen
Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
Cardiovascular Therapeutics
title Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
title_full Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
title_fullStr Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
title_full_unstemmed Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
title_short Sodium Lactate Accelerates M2 Macrophage Polarization and Improves Cardiac Function after Myocardial Infarction in Mice
title_sort sodium lactate accelerates m2 macrophage polarization and improves cardiac function after myocardial infarction in mice
url http://dx.doi.org/10.1155/2021/5530541
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