Role In Acute Myocardial Infarction Research Articles

Chemerin in the Spotlight: Revealing Its Multifaceted Role in Acute Myocardial Infarction.

Chemerin, an adipokine known for its role in adipogenesis and inflammation, has emerged as a significant biomarker in cardiovascular diseases, including acute myocardial infarction (AMI). Recent studies have highlighted chemerin's involvement in the pathophysiological processes of coronary artery disease (CAD), where it modulates inflammatory responses, endothelial function, and vascular remodelling. Elevated levels of chemerin have been associated with adverse cardiovascular outcomes, including increased myocardial injury, left ventricular dysfunction, and heightened inflammatory states post-AMI. This manuscript aims to provide a comprehensive review of the current understanding of chemerin's role in AMI, detailing its molecular mechanisms, clinical implications, and potential as a biomarker for diagnosis and prognosis. Additionally, we explore the therapeutic prospects of targeting chemerin pathways to mitigate myocardial damage and improve clinical outcomes in AMI patients. By synthesizing the latest research findings, this review seeks to elucidate the multifaceted role of chemerin in AMI and its promise as a target for innovative therapeutic strategies.

FASLG as a Key Member of Necroptosis Participats in Acute Myocardial Infarction by Regulating Immune Infiltration.

Acute myocardial infarction (AMI) is a major cause of human health risk. Necroptosis is a newly and recently reported mode of cell death, whose role in AMI has not been fully elucidated. This study aimed to search for necroptosis biomarkers associated with the occurrence of AMI and to explore their possible molecular mechanisms through bioinformatics analysis. The dataset GSE48060 was used to perform weighted gene co-expression network analysis (WGCNA) and differential analysis. Key modules, differential genes, and necroptosis-related genes (NRGs) were intersected to obtain candidate biomarkers. Groups were classified and differentially analyzed according to the expression of the key biomarker. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene set enrichment analysis (GSEA), and construction of protein-protein interaction (PPI) networks are performed on differentially expressed genes (DEGs). Finally, CIBERSORT was used to assess immune cell infiltration in AMI and the correlation of key biomarkers with immune cells. Immune cell infiltration analysis revealed the correlation between FASLG and multiple screened immune cells. WGCNA determined that the MEsaddlebrown module was the most significantly associated with AMI. Intersecting it with DEGs as well as NRGs, we obtained two key genes, FASLG and IFNG. But only FASLG showed statistically significant differences between the AMI group and the normal control group. Further analysis suggested that the down-regulation of FASLG may exert its function through the regulation of the central genes CD247 and YES1. Furthermore, FASLG was positively correlated with T-cell CD4 memory activation and T-cell gamma delta, and negatively correlated with macrophage M0. In conclusion, FASLG and its regulatory genes CD247 and YES1 might be involved in the development of AMI by regulating immune cell infiltration. FASLG might be a potential biomarker for AMI and provides a new direction for the diagnosis of AMI.

Ecliptasaponin A protects heart against acute ischemia-induced myocardial injury by inhibition of the HMGB1/TLR4/NF-κB pathway

Ethnopharmacological relevanceEclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.), has been demonstrated to exert superior anti-inflammatory activity against many inflammatory disorders. Aim of the studyInflammation plays a critical role in acute myocardial infarction (AMI). This study aims to explore the treatment effects of ESA in AMI, as well as the underlying mechanism. MethodsAn AMI mouse model was established in mice via left anterior descending coronary artery (LAD) ligation. After surgery, ESA was injected at doses of 0.5, 1.25, and 2.5 mg/kg, respectively. Myocardial infarction size, cardiomyocyte apoptosis and cardiac echocardiography were studied. The potential mechanism of action of ESA was investigated by RNA-seq, Western blot, surface plasmon resonance (SPR), molecular docking, and immunofluorescence staining. ResultsESA treatment not only significantly reduced myocardial infarct size, decreased myocardial cell apoptosis, and inhibited inflammatory cell infiltration, but also facilitated to improve cardiac function. RNA-seq and Western blot analysis proved that ESA treatment-induced differential expression genes mainly enriched in HMGB1/TLR4/NF-κB pathway. Consistently, ESA treatment resulted into the down-regulation of IL-1β, IL-6, and TNF-α levels after AMI. Furthermore, SPR and molecular docking results showed that ESA could bind directly to HMGB1, thereby impeding the activation of the downstream TLR4/NF-κB pathway. The immunofluorescence staining and Western blot results at the cellular level also demonstrated that ESA inhibited the activation of the HMGB1/TLR4/NF-κB pathway in H9C2 cells. ConclusionOur study was the first to demonstrate a cardiac protective role of ESA in AMI. Mechanism study indicated that the treatment effects of ESA are mainly attributed to its anti-inflammatory activity that was mediated by the HMGB1/TLR4/NF-κB pathway.

Identification of hub glycolysis-related genes in acute myocardial infarction and their correlation with immune infiltration using bioinformatics analysis

PurposeGlycolysis and immune metabolism play important roles in acute myocardial infarction (AMI). Therefore, this study aimed to identify and experimentally validate the glycolysis-related hub genes in AMI as diagnostic biomarkers, and further explore the association between hub genes and immune infiltration.MethodsDifferentially expressed genes (DEGs) from AMI peripheral blood mononuclear cells (PBMCs) were analyzed using R software. Glycolysis-related DEGs (GRDEGs) were identified and analyzed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) for functional enrichment. A protein–protein interaction network was constructed using the STRING database and visualized using Cytoscape software. Immune infiltration analysis between patients with AMI and stable coronary artery disease (SCAD) controls was performed using CIBERSORT, and correlation analysis between GRDEGs and immune cell infiltration was performed. We also plotted nomograms and receiver operating characteristic (ROC) curves to assess the predictive accuracy of GRDEGs for AMI occurrence. Finally, key genes were experimentally validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting using PBMCs.ResultsA total of 132 GRDEGs and 56 GRDEGs were identified on the first day and 4–6 days after AMI, respectively. Enrichment analysis indicated that these GRDEGs were mainly clustered in the glycolysis/gluconeogenesis and metabolic pathways. Five hub genes (HK2, PFKL, PKM, G6PD, and ALDOA) were selected using the cytoHubba plugin. The link between immune cells and hub genes indicated that HK2, PFKL, PKM, and ALDOA were significantly positively correlated with monocytes and neutrophils, whereas G6PD was significantly positively correlated with neutrophils. The calibration curve, decision curve analysis, and ROC curves indicated that the five hub GRDEGs exhibited high predictive value for AMI. Furthermore, the five hub GRDEGs were validated by RT-qPCR and western blotting.ConclusionWe concluded that HK2, PFKL, PKM, G6PD, and ALDOA are hub GRDEGs in AMI and play important roles in AMI progression. This study provides a novel potential immunotherapeutic method for the treatment of AMI.

Identification of diagnostic signature and immune infiltration for ischemic cardiomyopathy based on cuproptosis-related genes through bioinformatics analysis and experimental validation

BackgroundIschemic cardiomyopathy (IC) is primarily due to long-term ischemia/hypoxia of the coronary arteries, leading to impaired cardiac contractile or diastolic function. A new form of cell death induced by copper, called “cuproptosis” is related to the development and progression of multiple diseases. The cuproptosis-related gene (CuGs) plays an important role in acute myocardial infarction, while the specific mechanisms of CuGs in ischemic cardiomyopathy remain unclear. MethodsThe expressions of CuGs and their immune characteristics were analyzed with the IC datasets obtained from the Gene Expression Omnibus, namely GSE5406 and GSE57338, identifying core genes associated with IC development. By comparing RF, SVM, GLM and XGB models, the optimal machine learning model was selected. The expression of marker genes was validated based on the GSE57345, GSE48166 and GSE42955 datasets. Construct a CeRNA network based on core genes. Therapeutic chemiacals targeting core genes were acquired using the CTD database, and molecular docking was performed using Autodock vina software. By ligating the left anterior descending (LAD) coronary artery, an IC mouse model is established, and core genes were experimentally validated using Western blot (WB) and immunohistochemistry (IHC) methods. ResultsWe identified 14 CuGs closely associated with the onset of IC. The SVM model exhibited superior discriminative power (AUC = 0.914), with core genes being DLST, ATP7B, FDX1, SLC31A1 and DLAT. Core genes were validated on the GSE42955, GSE48166 and GSE57345 datasets, showing excellent performance (AUC = 0.943, AUC = 0.800, and AUC = 0.932). The CeRNA network consists of 218 nodes and 264 lines, including 5 core diagnostic genes, 52 miRNAs, and 161 lncRNAs. Chemicals predictions indicated 8 chemicals have therapeutic effects on the core diagnostic genes, with benzo(a)pyrene molecular docking showing the highest affinity (-11.3 kcal/mol). Compared to the normal group, the IC group,which was established by LAD ligation, showed a significant decrease in LVEF as indicated by cardiac ultrasound, and increased fibrosis as shown by MASSON staining, WB results suggest increased expression of DLST and ATP7B, and decreased expression of FDX1, SLC31A1 and DLAT in the myocardial ischemic area (p < 0.05), which was also confirmed by IHC in tissue sections. ConclusionIn summary, this study comprehensively revealed that DLST, ATP7B, FDX1, SLC31A1 and DLAT could be identified as potential immunological biomarkers in IC, and validated through an IC mouse model, providing valuable insights for future research into the mechanisms of CuGs and its diagnostic value to IC.

Exploring T-cell exhaustion features in Acute myocardial infarction for a Novel Diagnostic model and new therapeutic targets by bio-informatics and machine learning

BackgroundT-cell exhaustion (TEX), a condition characterized by impaired T-cell function, has been implicated in numerous pathological conditions, but its role in acute myocardial Infarction (AMI) remains largely unexplored. This research aims to identify and characterize all TEX-related genes for AMI diagnosis.MethodsBy integrating gene expression profiles, differential expression analysis, gene set enrichment analysis, protein-protein interaction networks, and machine learning algorithms, we were able to decipher the molecular mechanisms underlying TEX and its significant association with AMI. In addition, we investigated the diagnostic validity of the leading TEX-related genes and their interactions with immune cell profiles. Different types of candidate small molecule compounds were ultimately matched with TEX-featured genes in the “DrugBank” database to serve as potential therapeutic medications for future TEX-AMI basic research.ResultsWe screened 1725 differentially expressed genes (DEGs) from 80 AMI samples and 71 control samples, identifying 39 differential TEX-related transcripts in total. Functional enrichment analysis identified potential biological functions and signaling pathways associated with the aforementioned genes. We constructed a TEX signature containing five hub genes with favorable prognostic performance using machine learning algorithms. In addition, the prognostic performance of the nomogram of these five hub genes was adequate (AUC between 0.815 and 0.995). Several dysregulated immune cells were also observed. Finally, six small molecule compounds which could be the future therapeutic for TEX in AMI were discovered.ConclusionFive TEX diagnostic feature genes, CD48, CD247, FCER1G, TNFAIP3, and FCGRA, were screened in AMI. Combining these genes may aid in the early diagnosis and risk prediction of AMI, as well as the evaluation of immune cell infiltration and the discovery of new therapeutics.

Correlation of circulating fibroblast growth factor 21 levels with inflammatory factors and the degree of coronary artery stenosis in patients with acute myocardial infarction

BackgroundFibroblast growth factor 21 (FGF21) is a secreted protein that plays an important role in atherosclerosis and pathological cardiac remodeling. However, the correlation between FGF21 and the degree of coronary artery stenosis and its potential role in acute myocardial infarction (AMI) remain unclear. We examined whether changes in FGF21 levels in AMI correlate with the degree of coronary artery stenosis and the levels of inflammatory factors, and preliminarily investigated the effects of FGF21 on inflammatory factor levels and myocardial injury in rats with AMI. MethodsSerum levels of FGF21 and inflammatory factors in the AMI group and control group were measured, and the correlation between FGF21 and clinical indicators and inflammatory factors was analyzed. The effects of FGF21 on cardiac function and inflammatory response were evaluated through echocardiography and measurement of inflammatory factors. ResultsMultivariate logistic regression analysis showed that neutrophil percentage (NEUT%, odds ratio [OR]: 1.232; 95 % confidence interval [CI]: 1.028–1.477; p = 0.024) and FGF21 levels (OR: 2.063; 95 % CI: 1.187–3.586; p = 0.01) had independent effects on AMI. Spearman's rank correlation test showed that FGF21 levels were positively correlated with leukocyte count, NEUT%, neutrophil count, neutrophil to lymphocyte ratio, C-reactive protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and Gensini scores (p < 0.01), but negatively correlated with lymphocyte count (p < 0.01). FGF21 levels in myocardial tissues and serum levels of FGF21, IL-6, TNF-a, and MCP-1 were significantly higher in AMI rats than in the sham-operated group (p < 0.01). After overexpression of FGF21, serum levels of IL-6, TNF-a, and MCP-1 in rats were significantly decreased (p < 0.01), and cardiac function improved significantly. ConclusionsFGF21 levels were independently associated with AMI and may be related to the severity of coronary artery stenosis. Overexpression of FGF21 reduced serum inflammatory factor levels and improved cardiac function in AMI rats.

Exploring the Landscape of Anti-Inflammatory Trials: A Comprehensive Review of Strategies for Targeting Inflammation in Acute Myocardial Infraction.

The role of inflammation in the pathophysiology of acute myocardial infarction (AMI) is well established. In recognizing inflammation's pivotal role in AMI, this manuscript systematically traces the historical studies spanning from early attempts to the present landscape. Several anti-inflammatory trials targeting inflammation in post-AMI have been performed, and this review includes the key trials, as well as examines their designs, patient demographics, and primary outcomes. Efficacies and challenges are analyzed, thereby shedding light on the translational implications of trial outcomes. This article also discusses emerging trends, ongoing research, and potential future directions in the field. Practical applications and implications for clinical practice are considered by providing a holistic view of the evolving landscape of anti-inflammatory interventions in the context of AMI.

Differential Role of Factor XIII in Acute Myocardial Infarction and Ischemic Stroke.

Factor XIII is a transglutaminase enzyme that plays a crucial role in hemostasis and wound healing. It crosslinks fibrin strands, stabilizing clots and promoting clot resistance to fibrinolysis. Additionally, Factor XIII has been found to have multiple other functions that extend beyond coagulation, including the regulation of inflammation and tissue repair processes. Emerging evidence suggests that Factor XIII may also have differential roles in acute myocardial infarction and ischemic stroke, two common cardiovascular events with significant morbidity and mortality. In acute myocardial infarction, Factor XIII has been implicated in promoting clot stability and reducing the risk of re-occlusion. In ischemic stroke, Factor XIII may also contribute to the pathogenesis of cerebral ischemia by promoting clot formation and exacerbating neuronal damage. Several studies have investigated the association between Factor XIII and these cardiovascular events, using various approaches such as genetic polymorphism analysis, animal models, and clinical data analysis. These studies have provided important insights into the role of Factor XIII in acute myocardial infarction and ischemic stroke, highlighting its potential as a therapeutic target for interventions aimed at improving outcomes in these conditions. In this review, we will summarize the current understanding of Factor XIII's role in acute myocardial infarction and ischemic stroke.

Neutrophils are indispensable for adverse cardiac remodeling in heart failure

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both locally in failing myocardium (more in the border zone) and systemically in the blood, spleen, and bone marrow, together with increased BM granulopoiesis. There were heightened stimuli for neutrophil recruitment and trafficking in HF, with increased myocardial expression of the neutrophil chemoattract chemokines CXCL1 and CXCL5, and increased neutrophil chemotactic factors in the circulation. HF neutrophil NETotic activity was increased in vitro with coordinate increases in circulating neutrophil extracellular traps (NETs) in vivo. Neutrophil depletion with either antibody-based or genetic approaches abrogated the progression of LV remodeling and fibrosis at both intermediate and late stages of HF. Moreover, analogous to murine HF, the plasma milieu in human acute decompensated HF strongly promoted neutrophil trafficking. Collectively, these results support a key tissue-injurious role for neutrophils and their associated cytotoxic products in ischemic cardiomyopathy and suggest that neutrophils are potential targets for therapeutic immunomodulation in this disease.

CircRNA as an emerging role in acute myocardial infarction: a literature review

CircRNA as an emerging role in acute myocardial infarction: a literature review

Malat1 promotes macrophage-associated inflammation by increasing PPAR-γ methylation through binding to EZH2 in acute myocardial infarction

The inflammatory microenvironment of macrophage plays an important role in acute myocardial infarction (AMI), but the regulatory mechanism is unknown. Here, we aimed to investigate the role of Malat1 on inflammation microenvironment of macrophage in AMI. Our study found that Malat1 expression was increased in AMI, which mainly expressed in macrophages. Malat1 inhibition improved collagen deposition and inflammation in infarcted heart. In vitro, Malat1 inhibition evidently reduced macrophage-associated inflammation. The results from ribonucleic acid pull-down (RNA pull-down) and RNA Immunoprecipitation (RIP) assay demonstrated that Malat1 directly binds to EZH2. Malat1 and EZH2 complex could increase histone H3K27me3 expression and further inhibit the production of PPAR-γ. In vivo, inhibition of Malat1 also leaded to the down-regulation of both EZH2 and H3K27me3, as well as up-regulation of PPAR-γ in infarcted heart. Therefore, these findings demonstrate a novel mechanism of Malat1 on inflammation microenvironment of macrophage in AMI, which provide a new target for its treatment.

EGCG attenuated acute myocardial infarction by inhibiting ferroptosis via miR-450b-5p/ACSL4 axis

BackgroundEpigallocatechin gallate (EGCG) has multiple biological effects such as anti-tumor multiple drug resistance, antioxidation and anti-inflammatory properties. Ferroptosis is the main driving factor of ischemic heart injury, thus inhibiting ferroptosis may prove to be an effective treatment strategy for cardiovascular diseases. However, the role of EGCG on ferroptosis in ischemic myocardium and underlying mechanisms remain uncertain. PurposeThis study was aimed to investigate the effects and potential mechanisms of EGCG on myocardial ischemic-induced ferroptosis both in vitro and in vivo. MethodsCardiomyocyte hypoxia model and mouse acute myocardial infarction (AMI) model were established in vitro and in vivo. MiR-450b-5p and ACSL4 silencing or overexpression plasmids were transfected, with or without EGCG pretreatment. Cell viability was determined by the CCK-8 assay. Hematoxylin and eosin (HE) staining and transmission electron microscopy (TEM) were used to evaluate the morphologic alterations. TTC staining was used to observe the infarction area, and echocardiography was adopted to appraise the heart function. Using flow cytometry, the presence of reactive oxygen species (ROS) was assessed. The content of cardiac troponin I (cTn I), glutathione (GSH), malondialdehyde (MDA), divalent iron ions (Fe2+) and superoxide dismutase (SOD) were detected using reagent kits. A luciferase activity assay was performed to assess the binding ability of miR-450b-5p to ACSL4. Expressions of related genes and proteins were measured by RT-qPCR and western blotting respectively. ResultsEGCG attenuated AMI-induced ferroptosis and improved myocardial ischemia injury, which was associated with reducing iron deposition and cTn I, inhibition of lipid peroxidation, decreasing TFR1 and ACSL4, and upregulating SLC7A11, FTH1 and GPX4. Meanwhile, EGCG pretreatment increased miR-450b-5p expression in ischemic myocardium. Further researches discovered that knockdown of miR-450b-5p partially compromised EGCG-generated protective effect in hypoxia HL-1 cells, while combination with miR-450b-5p mimic could strengthen the potency of EGCG on ischemic myocardium. The dual-luciferase test demonstrated that miR-450b-5p has binding to ACSL4. Furthermore, silencing of ACSL4 synergistically increased the cardioprotective effect of EGCG. More significantly, EGCG treatment regulated the ferroptosis-related proteins expression via miR-450b-5p/ACSL4 axis. ConclusionIn summary, the present study evidently demonstrated that EGCG attenuates myocardial ischemia injury by targeting ferroptosis. Our work revealed the role of miR-450b-5p/ACSL4 axis in AMI for the first time. Further, it also elucidated the molecular mechanisms of EGCG on inhibiting ferroptosis greatly depend on the miR-450b-5p/ACSL4 axis, suggesting that EGCG may act as a novel anti-ferroptosis agent and exert a therapeutic role in AMI.

Recruitment of myeloid‑derived suppressor cells and regulatory T‑cells is associated with the occurrence of acute myocardial infarction.

The roles of myeloid-derived suppressor cells (MDSCs) and regulatory T-cells (Tregs) in acute myocardial infarction (AMI) remain elusive. The present study aimed to analyze the proportions of the granulocytic and monocytic populations of MDSCs (G-MDSCs and M-MDSCs, respectively), and Tregs in the peripheral blood mononuclear cells (PBMCs) of patients with AMI. The present study recruited 34 patients with AMI and 37 healthy controls without clinical signs of myocardial ischemia. PBMCs were isolated from the peripheral blood samples of patients with AMI within 24 h following admission to the hospital and from those of the healthy controls during a physical examination. Two subsets of MDSCs, G-MDSCs (CD15+CD33+CD11b+CD14-HLA-DRlow) and M-MDSCs (CD14+CD15-CD11b+HLA-DRlow), and Tregs (CD3+CD4+CD25highCD127low T-cells) in the PBMCs derived from the patients with AMI and healthy controls were analyzed using flow cytometry. The effects of MDSCs derived from patients with AMI on naïve CD4+ T-cells were examined in the co-culture system. The results revealed that the proportions of G-MDSCs and M-MDSCs were higher in the peripheral blood of patients with AMI than in that of the healthy controls. The patients with AMI had significantly higher numbers of programmed death-ligand (PD-L)1- and PD-L2-positive G-MDSCs and M-MDSCs compared with the healthy controls (P<0.05). The MDSCs could acquire a granulocytic phenotype following AMI, and the G-MDSCs and M-MDSCs would be more likely to express PD-L2 and PD-L1, respectively. The ratios of Tregs to CD4+ T-cells and PD-1+ Tregs in the peripheral blood of patients with AMI were significantly higher than those in the healthy controls (P<0.05). The results of flow cytometry demonstrated an increase in the numbers of inducible Tregs in the co-culture system with the G-MDSCs derived from patients with AMI compared with the G-MDSCs derived from the healthy controls (P<0.01). On the whole, the findings presented herein demonstrate the accumulation of MDSCs, and the upregulation of PD-L1 and PD-L2 expression on the surface of MDSCs in patients with AMI. MDSCs can induce the expansion of Tregs by binding PD-1 on the surface of Tregs, thus playing a crucial role in AMI.

Clusterin regulates TRPM2 to protect against myocardial injury induced by acute myocardial infarction injury

BackgroundClusterin and transient receptor potential melastatin 2 (TRPM2) play significant roles in acute myocardial infarction (AMI), but their interactions in AMI are unclear. MethodsMyocardial infarction was induced by ligation of the left anterior descending coronary artery in wild-type C57BL/6J male mice. Infarct size and myocardium pathology were evaluated after 6, 12, and 24 h of ischemia. The expression levels of clusterin and TRPM2 were measured in the myocardium. Furthermore, myocardial infarction was induced in TRPM2 knockout (TRPM2-/-) C57BL/6J male mice to evaluate the expression of clusterin. H9C2 cells with various levels of TRPM2 expression were used to analyze the effects of clusterin under hypoxic conditions. ResultsFollowing AMI, myocardial hypertrophy and TRPM2 expression increased in a time-dependent manner. In contrast, the expression of clusterin decreased in an infarct time-dependent manner. Knockout of TRPM2 protected against myocardial injury and resulted in upregulation of clusterin. In the H9C2 cells, cultured under hypoxic conditions treatment with clusterin or silencing of TRPM2 significantly increased cell viability and decreased TRPM2 expression. Treatment with clusterin protected against TRPM2 overexpression-induced damage in hypoxia-treated H9C2 cells. ConclusionThis study characterized the effects of clusterin on TRPM2 in AMI, which may guide development of new treatment strategies for AMI.

Hypoxia Induces M2 Macrophages to Express VSIG4 and Mediate Cardiac Fibrosis After Myocardial Infarction.

M2 macrophage-mediated tissue repair plays an important role in acute myocardial infarction (AMI). Additionally, VSIG4, which is mainly expressed on tissue-resident and M2 macrophages, is crucial for the regulation of immune homeostasis; however, its effects on AMI remain unknown. In this study, we aimed to investigate the functional significance of VSIG4 in AMI using VSIG4 knockout and adoptive bone marrow transfer chimeric models. We also determined the function of cardiac fibroblasts (CFs) through gain- or loss-of-function experiments. We showed that VSIG4 promotes scar formation and orchestrates the myocardial inflammatory response after AMI, while also promoting TGF-β1 and IL-10. Moreover, we revealed that hypoxia promotes VSIG4 expression in cultured bone marrow M2 macrophages, ultimately leading to the conversion of CFs to myofibroblasts. Our results reveal a crucial role for VSIG4 in the process of AMI in mice and provide a potential immunomodulatory therapeutic avenue for fibrosis repair after AMI.

Activation of PTEN/P13K/AKT Signaling Pathway by miRNA-124-3p-Loaded Nanoparticles to Regulate Oxidative Stress Attenuates Cardiomyocyte Regulation and Myocardial Injury.

As a common cardiovascular disease, acute myocardial infarction seriously affects the health and life of patients. miRNAs play an important role in acute myocardial infarction. Based on miRNA obtained from the previous sequencing, this study investigated whether miRNA (miR)-124-3p-loaded nanoparticles (NPs) affect the phenotype of the acute myocardial infarction (AMI) rat. Nano-miR-124-3p decreased the myocardial infarction area, improved the myocardial tissue structure, and increased the degree of fibrosis. Nano-miR-124-3p decreased apoptosis and the expression of cleaved caspase 3, indicating its role in protecting and repairing the myocardium. To further verify the action mechanism of miRNA, a potential target gene of miR-124-3p, PTEN was identified by STARBASE and further confirmed using double luciferase assays. Following cotransfection of nano-miR-124-3p and PTEN, the areas of tissue structure damage, myocardial infarction, and fibrosis were substantially elevated. The expression of cleaved caspase 3 and the apoptosis rate in the nano-miR-124-3p and PTEN cotransfection group was also significantly increased. Bioinformatics analysis revealed that miRNA-124-3 may regulate oxidative stress injury by targeting PTEN. Taken together, miR-124-3p could protect and repair myocardial tissues through targeting PTEN.

Integrated Analysis and Validation of Autophagy-Related Genes and Immune Infiltration in Acute Myocardial Infarction.

Background Acute myocardial infarction (AMI) is one of the most critical conditions of coronary heart disease with many uncertainties regarding reduction of ischemia/reperfusion injury, medical treatment strategies, and other aspects. The inflammatory immune response has a bidirectional regulatory role in AMI and plays an essential role in myocardial remodeling after AMI. The purpose of our research was tantamount to explore possible mechanisms of AMI and to analyze the relationship with the immune microenvironment. Methods We firstly analyzed the expression profile of GSE61144 and HADb to identify differentially expressed autophagy-related genes (DEARGs). Then, we performed GO, functional enrichment analysis, and constructed PPI network by Metascape. A lncRNA-miRNA-mRNA ceRNA network was built, and hub genes were extracted by Cytoscape. After that, we used CIBERSORT algorithm to estimate the proportion of immunocytes, followed by correlation analysis to find relationships between hub DEARGs and immunocyte subsets. Finally, we verified those hub genes in another dataset and cellular experiments qPCR. Results Compared with controls, we identified 44 DEARGs and then filtered the genes of MCODE by constructing PPI network for further analysis. A total of 45 lncRNAs, 24 miRNAs, 19 mRNAs, 162 lncRNA-miRNA pairs, and 37 mRNA-miRNA pairs were used to construct a ceRNA network, and 4 hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) were extracted. We then estimated 5 classes of immunocytes that differed between AMI and controls. According to the results of correlation analysis, these 4 hub DEARGs may play modulatory effects in immune infiltrating cells, notably in CD8+ T cells and neutrophils. Finally, the same results were verified in GSE60993 and qPCR experiments. Conclusion Our findings suggest that those hub DEARGs (BCL2, MAPK1, RAF1, and PRKAR1A) and immunocytes probably play functions in the progression of AMI, providing potential diagnostic markers and new perspectives for treatment of AMI.

MicroRNAs Expression Profile in Young Patients with Acute Myocardial Infarction

Introduction: Acute myocardial infarction (AMI) is a severe coronary heart disease. Targeted miRNAs studies implicated two main pathways in the regulation of AMI namely pro-apoptosis (miR-29b and miR-194-5p on PTEN) and pro-necroptosis (miR-325 &amp; miR-105 on RIPK3 ) pathways. This study aims to profile the miRNAs in Healthy Controls, Young AMI, and Mature AMI patients with matching criteria. MATERIALS AND Methods: Total RNA was extracted from plasma and the miRNA expression profiling using small RNA was done on the BGISEQ500 SE5 sequencing platform with BGI sequencing libraries. The sequence data were analysed using Gene Ontology (GO) to determine the function of the differently expressed genes, while Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were applied to identify the biological pathways in Young AMI against Mature AMI. Results: Of 1497 differentially expressed miRNAs, 1090 miRNAs were upregulated, and 407 miRNAs were downregulated in Young AMI against Mature AMI. The top 10 upregulated miRNAs were miR-552, miR-4446-3p, miR-432-5p, miR-548j-5p, miR-219, miR-982, miR-181a-2-3p, miR-654-5p, miR-58 and miR-548k; while the top 10 downregulated were miR-16-5p, miR-1064, miR-431-5p, miR-790 miR-1177, miR-201, miR-105, miR-518, miR-419 and miR-1103. There were 9 novel miRNAs discovered in this study; miR-58, miR-982, miR-548k, miR-1064, miR-790, miR-1177, miR-201, miR-419, and miR-1103. The target genes of differentially expressed miRNAs that were mapped to the signal transduction pathway in KEGG indicated that 346 classes were enriched. Conclusion: Our miRNA profiling revealed differentially expressed miRNAs including 9 novel miRNAs in Young and Mature AMI that require further evaluations for their roles in AMI.

Inflammation and Oxidative Stress Role of S100A12 as a Potential Diagnostic and Therapeutic Biomarker in Acute Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases with high morbidity and mortality. Numerous studies have indicated that S100A12 may has an essential role in the occurrence and development of AMI, and in-depth studies are currently lacking. The purpose of this study is to investigate the effect of S100A12 on inflammation and oxidative stress and to determine its clinical applicability in AMI. Here, AMI datasets used to explore the expression pattern of S100A12 in AMI were derived from the Gene Expression Omnibus (GEO) database. The pooled standard average deviation (SMD) was calculated to further determine S100A12 expression. The overlapping differentially expressed genes (DEGs) contained in all included datasets were recognized by the GEO2R tool. Then, functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were carried out to determine the molecular function of overlapping DEGs. Gene set enrichment analysis (GSEA) was conducted to determine unrevealed mechanisms of S100A12. Summary receiver operating characteristic (SROC) curve analysis and receiver operating characteristic (ROC) curve analysis were carried out to identify the diagnostic capabilities of S100A12. Moreover, we screened miRNAs targeting S100A12 using three online databases (miRWalk, TargetScan, and miRDB). In addition, by comprehensively using enzyme-linked immunosorbent assay (ELISA), real-time quantitative PCR (RT-qPCR), Western blotting (WB) methods, etc., we used the AC16 cells to validate the expression and underlying mechanism of S100A12. In our study, five datasets related to AMI, GSE24519, GSE60993, GSE66360, GSE97320, and GSE48060 were included; 412 overlapping DEGs were identified. Protein-protein interaction (PPI) network and functional analyses showed that S100A12 was a pivotal gene related to inflammation and oxidative stress. Then, S100A12 overexpression was identified based on the included datasets. The pooled standard average deviation (SMD) also showed that S100A12 was upregulated in AMI (SMD = 1.36, 95% CI: 0.70-2.03, p = 0.024). The SROC curve analysis result suggested that S100A12 had remarkable diagnostic ability in AMI (AUC = 0.90, 95% CI: 0.87-0.92). And nine miRNAs targeting S100A12 were also identified. Additionally, the overexpression of S100A12 was further confirmed that it maybe promote inflammation and oxidative stress in AMI through comprehensive in vitro experiments. In summary, our study suggests that overexpressed S100A12 may be a latent diagnostic biomarker and therapeutic target of AMI that induces excessive inflammation and oxidative stress. Nine miRNAs targeting S100A12 may play a crucial role in AMI, but further studies are still needed. Our work provides a positive inspiration for the in-depth study of S100A12 in AMI.