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

Jialiang Zhang,Li Chen,Wenhua Lei,Fangyang Huang,Guoyong Li,Changming Li,Yijian Li,Mao Chen,Yanbiao Liao,Jiahao Zhao,Christoph E Hagemeyer

doi:10.1155/2021/5530541

Jialiang Zhang, Li Chen + Show 9 more

Open Access

https://doi.org/10.1155/2021/5530541

Copy DOI

Abstract

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.

Highlights

Ischemic heart disease is the most common cause of death, and the frequency is increasing worldwide
These results indicated that sodium lactate could improve cardiac function after myocardial infarction (MI)
We determined the percentage of M2 macrophages in the total cell population by using immunofluorescence and flow cytometric analysis of MI heart tissue, and the results revealed that sodium lactate increased the M2 macrophage proportion three days after MI

Summary

Introduction

Ischemic heart disease is the most common cause of death, and the frequency is increasing worldwide. Cardiac repair after myocardial infarction (MI) is initiated by robust tissue inflammation, followed by active suppression and resolution. Macrophages are generally classified into two main phenotypes, proinflammatory (M1) and anti-inflammatory macrophages (M2). In the early period post-MI, the injured heart is dominated by proinflammatory macrophages, several days later, the anti-inflammatory macrophages take over. Anti-inflammatory macrophages perform key homeostatic functions that facilitate cardiac recovery and remodeling. 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. Sodium lactate facilitates anti-inflammatory M2 macrophage polarization and protects against MI by regulating P-STAT3

Methods

Results

Conclusion