Dirty Jobs: Macrophages at the Heart of Cardiovascular Disease

Stevens, Travis W.; Khalaf, Fatimah K.; Soehnlen, Sophia; Hegde, Prajwal; Storm, K; Meenakshisundaram, Chandramohan; Dworkin, Lance D.; Malhotra, Deepak; Kennedy, David J.; Dube, Prabhatchandra

doi:10.3390/biomedicines10071579

Cited by 7 publications

(4 citation statements)

References 151 publications

(241 reference statements)

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“…The expression of macrophages, CD4 + T cells, NK cells, plasma cells, and neutrophils in myocardial tissue is significantly different from the normal tissue ( Li et al, 2021 ). Consistent with previous findings, M2 macrophages are reduced in heart failure myocardial tissue, which in turn increases cardiac apoptosis and myocardial CD4 + T-cell accumulation ( Stevens et al, 2022 ). In contrast, neutrophils exert a deleterious function in an experimental model of heart failure induced by too much pressure ( Liu et al, 2021 ).…”

Section: Discussionsupporting

confidence: 92%

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Bian

2023

Front. Genet.

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Background: Heart failure (HF) is not only a common complication in patients with end-stage renal disease (ESRD) but also a major cause of death. Although clinical studies have shown that there is a close relationship between them, the mechanism of its occurrence is unclear. The aim of this study is to explore the molecular mechanisms between HF and ESRD through comprehensive bioinformatics analysis, providing a new perspective on the crosstalk between these two diseases.Methods: The HF and ESRD datasets were downloaded from the Gene Expression Omnibus (GEO) database; we identified and analyzed common differentially expressed genes (DEGs). First, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analyses (GSVA) were applied to explore the potential biological functions and construct protein−protein interaction (PPI) networks. Also, four algorithms, namely, random forest (RF), Boruta algorithm, logical regression of the selection operator (LASSO), and support vector machine-recursive feature elimination (SVM-RFE), were used to identify the candidate genes. Subsequently, the diagnostic efficacy of hub genes for HF and ESRD was evaluated using eXtreme Gradient Boosting (XGBoost) algorithm. CIBERSORT was used to analyze the infiltration of immune cells. Thereafter, we predicted target microRNAs (miRNAs) using databases (miRTarBase, TarBase, and ENOCRI), and transcription factors (TFs) were identified using the ChEA3 database. Cytoscape software was applied to construct mRNA−miRNA−TF regulatory networks. Finally, the Drug Signatures Database (DSigDB) was used to identify potential drug candidates.Results: A total of 68 common DEGs were identified. The enrichment analysis results suggest that immune response and inflammatory factors may be common features of the pathophysiology of HF and ESRD. A total of four hub genes (BCL6, CCL5, CNN1, and PCNT) were validated using RF, LASSO, Boruta, and SVM-RFE algorithms. Their AUC values were all greater than 0.8. Immune infiltration analysis showed that immune cells such as macrophages, neutrophils, and NK cells were altered in HF myocardial tissue, while neutrophils were significantly correlated with all four hub genes. Finally, 11 target miRNAs and 10 TFs were obtained, and miRNA−mRNA−TF regulatory network construction was performed. In addition, 10 gene-targeted drugs were discovered.Conclusion: Our study revealed important crosstalk between HF and ESRD. These common pathways and pivotal genes may provide new ideas for further clinical treatment and experimental studies.

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Section: Discussionsupporting

confidence: 92%

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Bian

2023

Front. Genet.

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“…A reduction in the macrophage inflammatory response has been associated with anti-atherogenic properties. Many potential macrophage-based treatments for cardiovascular disease target macrophage-produced proinflammatory cytokines [ 69 ].…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Crosstalk between Inflammation and Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Is There a Common Basis?

Sircana,

Erre,

Castagna

et al. 2024

Life

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Cardiovascular disease is the leading cause of morbidity and mortality in patients with rheumatoid arthritis and systemic lupus erythematosus. Traditional cardiovascular risk factors, although present in lupus and rheumatoid arthritis, do not explain such a high burden of early cardiovascular disease in the context of these systemic connective tissue diseases. Over the past few years, our understanding of the pathophysiology of atherosclerosis has changed from it being a lipid-centric to an inflammation-centric process. In this review, we examine the pathogenesis of atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis, the two most common systemic connective tissue diseases, and consider them as emblematic models of the effect of chronic inflammation on the human body. We explore the roles of the inflammasome, cells of the innate and acquired immune system, neutrophils, macrophages, lymphocytes, chemokines and soluble pro-inflammatory cytokines in rheumatoid arthritis and systemic lupus erythematosus, and the roles of certain autoantigens and autoantibodies, such as oxidized low-density lipoprotein and beta2-glycoprotein, which may play a pathogenetic role in atherosclerosis progression.

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“…Upon occurrence of MI, many blood monocytes infiltrate into the ischemic heart tissue and differentiate into macrophages [ 17 ]. Activated macrophages can be classified into two main categories: classically activated macrophage (M1 type) and alternative activated type (M2) [ 18 , 19 ]. In the early pathogenesis of MI, M1 macrophages produce several pro-inflammatory cytokines, such as IL-1β, IL-6, IL-12, TNF-α and chemokines involved in immune cell recruitment and inflammation responses [ 11 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Excretory/secretory products from Trichinella spiralis adult worms ameliorate myocardial infarction by inducing M2 macrophage polarization in a mouse model

Wu,

Yin,

Wen

et al. 2023

Parasites Vectors

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Background Ischemia-induced inflammatory response is the main pathological mechanism of myocardial infarction (MI)-caused heart tissue injury. It has been known that helminths and worm-derived proteins are capable of modulating host immune response to suppress excessive inflammation as a survival strategy. Excretory/secretory products from Trichinella spiralis adult worms (Ts-AES) have been shown to ameliorate inflammation-related diseases. In this study, Ts-AES were used to treat mice with MI to determine its therapeutic effect on reducing MI-induced heart inflammation and the immunological mechanism involved in the treatment. Methods The MI model was established by the ligation of the left anterior descending coronary artery, followed by the treatment of Ts-AES by intraperitoneal injection. The therapeutic effect of Ts-AES on MI was evaluated by measuring the heart/body weight ratio, cardiac systolic and diastolic functions, histopathological change in affected heart tissue and observing the 28-day survival rate. The effect of Ts-AES on mouse macrophage polarization was determined by stimulating mouse bone marrow macrophages in vitro with Ts-AES, and the macrophage phenotype was determined by flow cytometry. The protective effect of Ts-AES-regulated macrophage polarization on hypoxic cardiomyocytes was determined by in vitro co-culturing Ts-AES-induced mouse bone marrow macrophages with hypoxic cardiomyocytes and cardiomyocyte apoptosis determined by flow cytometry. Results We observed that treatment with Ts-AES significantly improved cardiac function and ventricular remodeling, reduced pathological damage and mortality in mice with MI, associated with decreased pro-inflammatory cytokine levels, increased regulatory cytokine expression and promoted macrophage polarization from M1 to M2 type in MI mice. Ts-AES-induced M2 macrophage polarization also reduced apoptosis of hypoxic cardiomyocytes in vitro. Conclusions Our results demonstrate that Ts-AES ameliorates MI in mice by promoting the polarization of macrophages toward the M2 type. Ts-AES is a potential pharmaceutical agent for the treatment of MI and other inflammation-related diseases. Graphical Abstract

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Dirty Jobs: Macrophages at the Heart of Cardiovascular Disease

Cited by 7 publications

References 151 publications

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Uncovering the molecular mechanisms between heart failure and end-stage renal disease via a bioinformatics study

Crosstalk between Inflammation and Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Is There a Common Basis?

Excretory/secretory products from Trichinella spiralis adult worms ameliorate myocardial infarction by inducing M2 macrophage polarization in a mouse model

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