Blocking the A &lt;sub&gt;2B&lt;/sub&gt; Adenosine Receptor Alleviates Myocardial Damage by Inhibiting Spleen-Derived MDSC Mobilization after Acute Myocardial Infarction

Yu, Zongying; Yang, Ling; Xu, Qiancheng; Cao, Yuhan; Tang, Shengxing; Fu, Cong

doi:10.2139/ssrn.3962887

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…The most correlated pair in cluster-2 is TET3-MDSC (correlation coefficient = 0.65, p < 0.001), while TET3-Mast cell (correlation coefficient = 0.59, p < 0.001) in cluster-1. MDSCs are pathologically activated monocytes and neutrophils with formidable immunosuppressive activity (54), and current studies found that MDSCs mobilization were closely related to AMI (55). By preventing the local inflammatory response and inflammation-mediated apoptosis, MDSCs may have a positive and protective effect on the process of ventricular remodeling after AMI (56).…”

Section: Discussionmentioning

confidence: 97%

5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy

Guo

Jiang

Wang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundMost deaths from coronary artery disease (CAD) are due to acute myocardial infarction (AMI). There is an urgent need for early AMI detection, particularly in patients with stable CAD. 5-methylcytosine (5mC) regulatory genes have been demonstrated to involve in the progression and prognosis of cardiovascular diseases, while little research examined 5mC regulators in CAD to AMI progression.MethodTwo datasets (GSE59867 and GSE62646) were downloaded from Gene Expression Omnibus (GEO) database, and 21 m5C regulators were extracted from previous literature. Dysregulated 5mC regulators were screened out by “limma.” The least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm were employed to identify hub 5mC regulators in CAD to AMI progression, and 43 clinical samples (Quantitative real-time PCR) were performed for expression validation. Then a logistic model was built to construct 5mC regulator signatures, and a series of bioinformatics algorithms were performed for model validation. Besides, 5mC-associated molecular clusters were studied via unsupervised clustering analysis, and correlation analysis between immunocyte and 5mC regulators in each cluster was conducted.ResultsNine hub 5mC regulators were identified. A robust model was constructed, and its prominent classification accuracy was verified via ROC curve analysis (area under the curve [AUC] = 0.936 in the training cohort and AUC = 0.888 in the external validation cohort). Besides, the clinical effect of the model was validated by decision curve analysis. Then, 5mC modification clusters in AMI patients were identified, along with the immunocyte infiltration levels of each cluster. The correlation analysis found the strongest correlations were TET3—Mast cell in cluster-1 and TET3-MDSC in cluster-2.ConclusionNine hub 5mC regulators (DNMT3B, MBD3, UHRF1, UHRF2, NTHL1, SMUG1, ZBTB33, TET1, and TET3) formed a diagnostic model, and concomitant results unraveled the critical impact of 5mC regulators, providing interesting epigenetics findings in AMI population vs. stable CAD.

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Section: Discussionmentioning

confidence: 97%

5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy

Guo

Jiang

Wang

et al. 2022

Front. Cardiovasc. Med.

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“…MDSCs were previously thought to play an important tumor-protective role in the tumor microenvironment ( 120 ), but our previous study found that splenic-derived MDSCs were heavily recruited and exacerbated myocardial injury within 24 hours after MI, and blockade of the A adenosine receptor (AAR) inhibited MDSCs mobilization, thereby improving cardiac systolic function ( 121 ). Thus, AAR-mediated mobilization of MDSCs may be a potential therapeutic target after MI, however, the exact mechanism remains to be elucidated.…”

Section: Powerful Modulation Of Ventricular Remodeling By Immune Cellsmentioning

confidence: 99%

Immune cells drive new immunomodulatory therapies for myocardial infarction: From basic to clinical translation

Nian

Huang

2023

Front. Immunol.

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The high incidence of heart failure secondary to myocardial infarction (MI) has been difficult to effectively address. MI causes strong aseptic inflammation, and infiltration of different immune cells and changes in the local inflammatory microenvironment play a key regulatory role in ventricular remodeling. Therefore, the possibility of improving the prognosis of MI through targeted immunity has been of interest and importance in MI. However, previously developed immune-targeted therapies have not achieved significant success in clinical trials. Here, we propose that the search for therapeutic targets from different immune cells may be more precise and lead to better clinical translation. Specifically, this review summarizes the role and potential therapeutic targets of various immune cells in ventricular remodeling after MI, especially monocytes/macrophages and neutrophils, as a way to demonstrate the importance and potential of immunomodulatory therapies for MI. In addition, we analyze the reasons for the failure of previous immunomodulatory therapies and the issues that need to be addressed, as well as the prospects and targeting strategies of using immune cells to drive novel immunomodulatory therapies, hoping to advance the development of immunomodulatory therapies by providing evidence and new ideas.

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Blocking the A <sub>2B</sub> Adenosine Receptor Alleviates Myocardial Damage by Inhibiting Spleen-Derived MDSC Mobilization after Acute Myocardial Infarction

Cited by 2 publications

References 36 publications

5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy

5mC modification patterns provide novel direction for early acute myocardial infarction detection and personalized therapy

Immune cells drive new immunomodulatory therapies for myocardial infarction: From basic to clinical translation

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