Study on the Mechanism of NLRP3/IL-1/ NF-κB Signaling Pathway and Macrophage Polarization in the Occurrence and Development of VTE

Abuduhalike, Refukaiti; Abudouwayiti, Aihaidan; Sun, Jing; Mahemuti, Ailiman

doi:10.1016/j.avsg.2022.09.056

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…Neutrophils undergo activation during the acute phase of DVT development; however, their numbers are likely to decline in the chronic phase due to depletion. Existing literature supports the significant role of macrophages in the pathogenesis and progression of both BD and VTE 56 – 58 . Inflammasome activation in macrophages leads to the release of tissue factor, a critical trigger for thrombosis 59 .…”

Section: Discussionmentioning

confidence: 79%

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Liu,

Wang,

et al. 2024

Sci Rep

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Behçet’s disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein–protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723–0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

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Section: Discussionmentioning

confidence: 79%

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Liu,

Wang,

et al. 2024

Sci Rep

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“…Macrophages can be categorized into two main subsets: the classical M1-type activation and the alternative M2-type activation. M1 macrophages, also known as the pro-inflammatory phenotype, are activated by various stimuli such as pathogen-associated molecular patterns (PAMPs) [73], danger-associated molecular patterns (DAMPs) [74,75], and pro-inflammatory cytokines like IL-1α [76], interferon-γ [77], and TNF-α [77,78]. These M1 polarized macrophages produce pro-inflammatory molecules, including IL-1, IL-6, IL-12, IL-23, iNOS, matrix metalloproteinase 12 (MMP12), and MINCLE [58,[79][80][81].…”

Section: Polarization Of Macrophages Within Diabetic Microenvironmentmentioning

confidence: 99%

Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease

Lin,

Yang,

et al. 2024

IJMS

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Diabetes is not solely a metabolic disorder but also involves inflammatory processes. The immune response it incites is a primary contributor to damage in target organs. Research indicates that during the initial phases of diabetic nephropathy, macrophages infiltrate the kidneys alongside lymphocytes, initiating a cascade of inflammatory reactions. The interplay between macrophages and other renal cells is pivotal in the advancement of kidney disease within a hyperglycemic milieu. While M1 macrophages react to the inflammatory stimuli induced by elevated glucose levels early in the disease progression, their subsequent transition to M2 macrophages, which possess anti-inflammatory and tissue repair properties, also contributes to fibrosis in the later stages of nephropathy by transforming into myofibroblasts. Comprehending the diverse functions of macrophages in diabetic kidney disease and regulating their activity could offer therapeutic benefits for managing this condition.

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“…Therefore, VTE is the result of the coagulation system's cascade reaction. [27][28][29] Coagulation factor XII (FXII), an essential coagulation factor, was found to be associated with thrombosis, the study revealed that the knockdown of FXII markedly raised superoxide dismutase (SOD) concentrations, reduced the thrombosis and apoptosis, and raised the malondialdehyde (MDA) concentrations in DVT mice. Moreover, TNFα, IL-6, interleukin-8 (IL-8), and phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) signaling activation were all markedly decreased by FXII knockdown.…”

Section: Inflammatory Factormentioning

confidence: 99%

Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism

Huang,

Xin,

Wang

et al. 2023

JIR

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Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.

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Study on the Mechanism of NLRP3/IL-1/ NF-κB Signaling Pathway and Macrophage Polarization in the Occurrence and Development of VTE

Cited by 6 publications

References 41 publications

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Exploration of effective biomarkers for venous thrombosis embolism in Behçet’s disease based on comprehensive bioinformatics analysis

Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease

Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism

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