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

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jialiang Zhang ◽  
Fangyang Huang ◽  
Li Chen ◽  
Guoyong Li ◽  
Wenhua Lei ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Flow Cytometric Analysis ◽  
Sodium Lactate ◽  
M2 Macrophage ◽  
Mrna Levels ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory

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.

scholarly journals Blockade of the Notch Signaling Pathway Promotes M2 Macrophage Polarization to Suppress Cardiac Fibrosis Remodeling in Mice With Myocardial Infarction

2022 ◽  
Vol 8 ◽  
Author(s):  
Zhi Li ◽  
Miao Nie ◽  
Liming Yu ◽  
Dengshun Tao ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Cardiac Fibrosis ◽  
Macrophage Polarization ◽  
Notch Signaling Pathway ◽  
Inflammatory Factors ◽  
M2 Macrophage ◽  
M2 Polarization

Myocardial infarction (MI) is regarded as a serious ischemic heart disease on a global level. The current study set out to explore the mechanism of the Notch signaling pathway in the regulation of fibrosis remodeling after the occurrence of MI. First, experimental mice were infected with recombination signal binding protein J (RBP-J) shRNA and empty adenovirus vector, followed by the establishment of MI mouse models and detection of cardiac function. After 4 weeks of MI, mice in the sh-RBP-J group were found to exhibit significantly improved cardiac function relative to the sh-NC group. Moreover, knockdown of RBP-J brought about decreased infarct area, promoted cardiac macrophages M2 polarization, reduced cardiac fibrosis, and further decreased transcription and protein expressions of inflammatory factors and fibrosis-related factors. Furthermore, downregulation of cylindromatosis (CYLD) using si-CYLD reversed the results that knockdown of RBP-J inhibited fibrogenesis and the release of inflammatory factors. Altogether, our findings indicated that the blockade of Notch signaling promotes M2 polarization of cardiac macrophages and improves cardiac function by inhibiting the imbalance of fibrotic remodeling after MI.

Nucleolin Improves Heart Function During Recovery From Myocardial Infarction by Modulating Macrophage Polarization

2021 ◽  
pp. 107424842198957
Author(s):  
Yuting Tang ◽  
Xiaofang Lin ◽  
Cheng Chen ◽  
Zhongyi Tong ◽  
Hui Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Early Phase ◽  
Heart Function ◽  
Macrophage Polarization ◽  
Late Phase ◽  
Macrophage Infiltration ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Nucleolin Expression

Background: Nucleolin has multiple functions within cell survival and proliferation pathways. Our previous studies have revealed that nucleolin can significantly reduce myocardial ischemia-reperfusion injury by promoting myocardial angiogenesis and reducing myocardial apoptosis. In this study, we attempted to determine the role of nucleolin in myocardial infarction (MI) injury recovery and the underlying mechanism. Methods: Male BALB/c mice aged 6–8 weeks were used to set up MI models by ligating the left anterior descending coronary artery. Nucleolin expression in the heart was downregulated by intramyocardial injection of a lentiviral vector expressing nucleolin-specific small interfering RNA. Macrophage infiltration and polarization were measured by real-time polymerase chain reaction, flow cytometry, and immunofluorescence. Cytokines were detected by enzyme-linked immunosorbent assay. Results: Nucleolin expression in myocardium after MI induction decreased a lot at early phase and elevated at late phase. Nucleolin knockdown impaired heart systolic and diastolic functions and decreased the survival rate after MI. Macrophage infiltration increased in the myocardium after MI. Most macrophages belonged to the M1 phenotype at early phase (2 days) and the M2 phenotype increased greatly at late phase after MI. Nucleolin knockdown in the myocardium led to a decrease in M2 macrophage polarization with no effect on macrophage infiltration after MI. Furthermore, Notch3 and STAT6, key regulators of M2 macrophage polarization, were upregulated by nucleolin in RAW 264.7 macrophages. Conclusions: Lack of nucleolin impaired heart function during recovery after MI by reducing M2 macrophage polarization. This finding probably points to a new therapeutic option for ischemic heart disease.

Immunomodulatory injectable silk hydrogels maintaining functional islets and promoting anti-inflammatory M2 macrophage polarization

Biomaterials ◽  
2018 ◽  
Vol 187 ◽  
pp. 1-17 ◽  
Author(s):  
Manishekhar Kumar ◽  
Prerak Gupta ◽  
Sohenii Bhattacharjee ◽  
Samit K. Nandi ◽  
Biman B. Mandal
Keyword(s):  
Macrophage Polarization ◽  
M2 Macrophage ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory

scholarly journals M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling

Diabetes ◽  
2015 ◽  
Vol 64 (8) ◽  
pp. 2836-2846 ◽  
Author(s):  
Woo Je Lee ◽  
Sanshiro Tateya ◽  
Andrew M. Cheng ◽  
Norma Rizzo-DeLeon ◽  
Nicholas F. Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Nitric Oxide Signaling ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Endothelial Nitric Oxide

scholarly journals IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation

2017 ◽  
Vol 112 (3) ◽  
Author(s):  
Mira Jung ◽  
Yonggang Ma ◽  
Rugmani Padmanabhan Iyer ◽  
Kristine Y. DeLeon-Pennell ◽  
Andriy Yabluchanskiy ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Remodeling ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Fibroblast Activation ◽  
M2 Macrophage Polarization

Supramolecular copolymer modified statins-loaded discoidal rHDLs for atherosclerotic anti-inflammatory therapy by cholesterol efflux and M2 macrophage polarization

2021 ◽  
Author(s):  
Qiqi Zhang ◽  
Jianhua He ◽  
Fengfei Xu ◽  
Xinya Huang ◽  
Yanyan Wang ◽  
...  
Keyword(s):  
Essential Role ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Cholesterol Removal ◽  
Atherosclerosis Progression ◽  
Inflammatory Phenotype ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

Foam cells with the pro-inflammatory macrophage phenotype (M1) play an essential role in atherosclerosis progression. Either cellular cholesterol removal or drug intervention was reported to polarize M1 into anti-inflammatory phenotype...

scholarly journals Dehydrocostus Lactone Attenuates Methicillin-Resistant Staphylococcus aureus-Induced Inflammation and Acute Lung Injury via Modulating Macrophage Polarization

2021 ◽  
Vol 22 (18) ◽  
pp. 9754
Author(s):  
Ya-Xian Wu ◽  
Feng-Juan Jiang ◽  
Gang Liu ◽  
Ying-Ying Wang ◽  
Zhi-Qi Gao ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
P38 Mapk ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Gram Positive Bacteria ◽  
M2 Macrophage Polarization ◽  
Anti Inflammatory ◽  
Dehydrocostus Lactone

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.

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