Frontiers in Cardiovascular Medicine最新文献

{"title":"Comparative analysis of prognostic assessment in hospitalized heart failure patients: a comprehensive evaluation of KDIGO and WRF classifications.","authors":"Chien-Hao Su, Pei-Chun Fan, Ya-Lien Cheng, Pao-Chu Wu, Chao-Yu Chen, Cheng-Chia Lee, Yung-Chang Chen, Victor Chien-Chia Wu, Pao-Hsien Chu, Chih-Hsiang Chang","doi":"10.3389/fcvm.2025.1447994","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1447994","url":null,"abstract":"<p><strong>Introduction: </strong>The definition of acute kidney dysfunction in patients with acute decompensated heart failure (ADHF) remains unclear. This study aimed to compare two sets of criteria for acute kidney injury (AKI), namely, the kidney disease: improving global outcomes (KDIGO) and worsening renal function (WRF) classification, in hospitalized patients with ADHF.</p><p><strong>Methods: </strong>We utilized a multi-institutional database with 17,684 cases of hospitalizations for HF. AKI was defined using KDIGO, WRF-serum creatinine (Scr), and WRF-estimated glomerular filtration rate (eGFR) criteria. The study compared the performance of these criteria in predicting in-hospital mortality and employed logistic regression to assess associations with mortality, HF hospitalization, and major adverse kidney effects (MAKE). A sensitivity analysis was conducted to compare the modified KDIGO (mKDIGO) with the traditional AKI criteria.</p><p><strong>Results: </strong>The incidences of ADHF according to the KDIGO, WRF-Scr, and WRF-eGFR criteria were 28.6%, 29.9%, and 29.9%, respectively. KDIGO exhibited higher discriminatory power compared with WRF-Scr and WRF-eGFR for in-hospital mortality[area under the curve (AUC):73.6% vs. 71.6% vs. 71.2%]. On all definitions, ADHF was predicted to have an increase in mortality and MAKE, with mortality increasing stepwise with AKI severity. A sensitivity analysis revealed mKDIGO to be more accurate than WRF criteria for identifying in-hospital mortality and recognizing AKI early.</p><p><strong>Conclusions: </strong>In hospitalized patients with ADHF, KDIGO is a more effective predictive tool for in-hospital mortality compared with WRF classification. Integrating a newer severity-staging classification into WRF criteria may enhance their predictive association with poor prognosis and enable early intervention.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1447994"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case Report: A <i>FBN1</i> frameshift-and-nonsense mutation and aortic dissection in Marfan syndrome.","authors":"Chao Su, Linjun Zeng, Haocheng Lu, Zanxin Wang, Minxin Wei","doi":"10.3389/fcvm.2025.1533138","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1533138","url":null,"abstract":"<p><strong>Background: </strong>Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder primarily affecting the cardiovascular, ocular, and skeletal systems. Cardiovascular complications are the leading cause of mortality in MFS. Mutations in the <i>FBN1</i> gene, which encodes fibrillin-1, a critical extracellular matrix protein, are the predominant cause of the disorder.</p><p><strong>Case presentation: </strong>On March 11, 2024, we diagnosed a 30-year-old female proband with MFS based on the revised Ghent criteria, presenting with aortic root aneurysm, aortic dissection, multiple skeletal abnormalities, and a family history of MFS. Whole-exome sequencing followed by Sanger sequencing confirmation identified a novel inherited insertion mutation (c.4991dupA) in exon 40 of the <i>FBN1</i> gene. We performed valve-sparing aortic root replacement (David Procedure) and total aortic arch replacement using a tetrafurcated graft, along with the implantation of a specially designed frozen elephant trunk in the descending aorta (Sun's Procedure). Postoperatively, the patient underwent biweekly clinical follow-ups for three months. No treatment-related adverse events were reported during the monitoring period.</p><p><strong>Conclusion: </strong>The diagnosis of MFS requires an integrated approach, combining clinical manifestations, imaging studies, and genetic analysis. This novel mutation is associated with severe skeletal manifestations and life-threatening cardiovascular abnormalities, underscoring its clinical relevance. Its association with aggressive phenotypes enhances genotype-phenotype correlations. Importantly, these findings highlight the imperative need for early intervention in high-risk individuals by bridging genetic discovery to clinical practice.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1533138"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of preoperative platelet counts with in-hospital mortality in patients with acute type A aortic dissection: a retrospective single-center study.","authors":"Yifei Zhou, Wuwei Wang, Quan Liu, Hongwei Jiang, Rui Fan, Xin Chen","doi":"10.3389/fcvm.2025.1524252","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1524252","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the relationship between preoperative platelet (PLT) count levels and postoperative in-hospital death and mid-term survival in patients with acute type A aortic dissection (ATAAD).</p><p><strong>Methods: </strong>A total of 341 ATAAD patients who underwent surgery between January 2019 and December 2023 were enrolled in this retrospective study. Preoperative PLT count levels were compared between the two groups for whether in-hospital death occurred. Then, patients were divided into two groups according to the optimal cutoff value by the maximum Youden index (184.5), and confounders were adjusted by multiple models to confirm whether low PLT count was an independent risk factor for in-hospital death after surgery. Kaplan-Meier method was used to draw the survival curve for the mid-term follow-up.</p><p><strong>Results: </strong>Patients who suffered in-hospital death had lower preoperative PLT count levels. After grouping by PLT count, patients in the low PLT count group exhibited higher in-hospital mortality (16.9% vs. 5.5%; <i>P</i> = 0.004). Univariate logistic regression analysis indicated that ATAAD patients with low PLT count were prone to death during hospitalization [odds ratio (OR): 4.549; 95% confidence interval (CI): 1.515-13.654, <i>p</i> < 0.05]. After adjustment for the potential confounders, low PLT count remained an independent risk factor with postoperative in-hospital death (OR: 3.443, 95%CI: 1.400-8.468, <i>p</i> < 0.05). Mid-term follow-up showed that there was a significant difference in overall survival between different PLT count groups (HR: 3.154; 95%CI: 1.495-6.654, <i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>A lower level of preoperative PLT count was an independent risk factor for in-hospital death in patients with ATAAD and had a lower survival rate at mid-term follow-up.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1524252"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Pre-interventional cardiac imaging.","authors":"Matthias Renker, Maxim Avanesov, Dominik Buckert","doi":"10.3389/fcvm.2025.1605768","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1605768","url":null,"abstract":"","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1605768"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving role of myocardial fibrosis in heart failure with preserved ejection fraction.","authors":"Muhammad K Malik, Menhel Kinno, Max Liebo, Mingxi D Yu, Mushabbar Syed","doi":"10.3389/fcvm.2025.1573346","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1573346","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) is a complex clinical diagnosis with a heterogeneous pathophysiology and clinical presentation. The hallmark of HFpEF is diastolic dysfunction associated with left ventricular remodeling and fibrosis. Myocardial interstitial fibrosis (MIF) occurs as the result of collagen deposition and is dependent on the underlying etiology of heart failure. Detection of MIF can be done by invasive histopathologic sampling or by imaging. More recently, novel biomarkers have been investigated as an alternative tool for not only the detection of MIF but also for the prognostication of patients with HFpEF which may in turn alleviate the need for invasive and expensive imaging in the future.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1573346"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture posttreatment attenuates the inflammatory injury in rats after MIRI through PPARγ/NF-κb pathway.","authors":"Xinxue Jiang, Chuchu Shen, Xing Li, Xuefeng Xia, Senlei Xu, Hongru Zhang","doi":"10.3389/fcvm.2025.1562285","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1562285","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to investigate the activation of the PPARγ/NF-κB pathway and its influence on macrophage M2 polarization induced by acupuncture at the Neiguan acupoint. Additionally, it seeks to explore the potential mechanisms by which electroacupuncture treatment may facilitate the reduction of inflammation in rats subjected to myocardial ischemia-reperfusion injury (MIRI).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;SD rats were randomly assigned to four groups: sham operation, model, electroacupuncture, and inhibitor, with 12 rats in each group. The left anterior descending branch of the coronary artery was ligated to establish the MIRI rat model. Electroacupuncture intervention at the bilateral Neiguan acupoints commenced 24 h post-chest closure, lasting for 30 min once daily over three consecutive days. Myocardial infarction was assessed through electrocardiography, while cardiac function was evaluated via echocardiography 24 h after modeling. The morphology and structure of myocardial tissues were examined using HE staining. Myocardial tissue levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were measured by ELISA in each group of rats. The expression of the M1 macrophage marker inducible nitric oxide synthase (iNOS) and the M2 macrophage marker arginase-1 (Arg-1) in myocardial tissues was analyzed using immunohistochemistry (IHC). Detection of macrophage polarization status in myocardial tissue by flow cytometry. Additionally, peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear transcription factor-κB (NF-κB) expression in myocardial tissues was assessed using Western blotting (WB).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the sham-operated group, rats in the model group exhibited a significant decrease in ejection fraction (EF) (&lt;i&gt;P&lt;/i&gt; &lt; 0.01), along with notable myocardial fiber damage characterized by inflammatory cell infiltration. Additionally, there was an elevated expression of IL-6, TGF-β, iNOS, CD-86 and phosphorylated p65 (p-p65) in myocardial tissue (&lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;P&lt;/i&gt; &lt; 0.05, &lt;i&gt;P&lt;/i&gt; &lt; 0.05 and &lt;i&gt;P&lt;/i&gt; &lt; 0.01, respectively). In contrast, rats in the electroacupuncture group demonstrated an increase in EF (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) compared to the model group. Myocardial fiber damage was significantly ameliorated, inflammatory cell infiltration was reduced. Furthermore, the expression of IL-10, TGF-β, Arg-1, CD-163 and PPARγ in cardiac muscle tissue was increased (&lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;P&lt;/i&gt; &lt; 0.01, &lt;i&gt;P&lt;/i&gt; &lt; 0.05, &lt;i&gt;P&lt;/i&gt; &lt; 0.05 and &lt;i&gt;P&lt;/i&gt; &lt; 0.01, respectively). Conversely, when compared to the electroacupuncture group, the EF of rats in the inhibitor group was significantly reduced (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), with pronounced myocardial fiber damage and accompanying inflammatory cell infiltration. Additionally, IL-6, TGF-β, iNOS CD-86 and p-p65 expression in myocardial tissue was increased (&lt;i&gt;P&lt;/","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1562285"},"PeriodicalIF":2.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology and experimental validation to investigate the mechanism of Gualou Xiebai Banxia decoction against myocardial ischemia.","authors":"Wanjun Zhu, Ping Shao, Ying Ren, Wenxuan Liu, Xiaorui Han, Kexin Zeng, Chunmei Dai, Feifei Liu","doi":"10.3389/fcvm.2025.1512791","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1512791","url":null,"abstract":"<p><strong>Background: </strong>Gualou Xiebai Banxia Decoction (GXBD), a traditional Chinese medicine, is used to treat myocardial ischemia (MI). However, the molecular mechanisms underlying its effects remain unclear. This study integrated network pharmacology and experimental validation to investigate the efficacy and potential mechanisms of GXBD in MI treatment.</p><p><strong>Methods: </strong>Network pharmacology was used to predict the mechanism of action of GXBD in MI. The predicted results were verified using ECG, echocardiography, HE staining, TTC staining, DHE, JC-1, immunofluorescence, and Western blot analysis in an isoproterenol (ISO)-induced MI rat model.</p><p><strong>Results: </strong>Network pharmacology identified 33 active components in GXBD and 139 potential targets against MI, with the PI3K/AKT signaling pathway playing a key role. Compared to the model group, GXBD improved the activities of BNP, CK-MB, and LDH, ameliorated the general condition and cardiac function, and repaired heart damage in MI rats. GXBD decreased MDA and ROS levels, increased SOD and GSH-Px levels, and protected cardiac tissues from oxidative stress. Moreover, GXBD increased ATP content, mitochondrial membrane potential, and the levels of p-PI3K, p-AKT, nuclear NRF2, and MFN2, while decreasing the levels of cytoplasmic NRF2 and DRP1.</p><p><strong>Conclusion: </strong>This study suggested that GXBD alleviates myocardial ischemia by ameliorating mitochondrial dysfunction through the PI3K/AKT/NRF2 signaling pathway.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1512791"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female sex is an independent risk factor for recurrence after ethanol Marshall bundle elimination in atrial fibrillation ablation.","authors":"Hongxu Chen, Xiong Xiong, Dan Chen, Xi Li, Liheng Yang, Zuowei Liu, Yanhong Chen, Jinlin Zhang","doi":"10.3389/fcvm.2025.1556222","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1556222","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) exhibits gender disparities in prevalence, complications, pharmacological management, and ablation efficacy. Ethanol infusion of the vein of Marshall (EIVOM) is promising for enhancing AF ablation success rate, yet sex differences of EIVOM are lacking evidence.</p><p><strong>Method: </strong>This was a non-randomized, single-center, retrospective observational study. Patients with AF received stepwise ablations composed of EIVOM, pulmonary vein isolation, and linear ablation. The primary endpoint was defined as the recurrence of atrial tachycardia over 30 s. Propensity score matching (PSM) was performed to reduce selection bias.</p><p><strong>Results: </strong>From April 2020 to May 2022, 432 patients were included, comprising 288 male patients and 144 female patients. Compared with the male patients, the female patients were older, with worse heart function class. EIVOM success rate was significantly lower in the female patients compared with the male patients (86.1% vs. 93.4%). No significant differences in major procedural complications were observed between the male and female patients. During a median follow-up of 12 months, the female patients had significantly higher AF recurrence. Multivariate Cox regression analysis showed that female sex, body mass index <21.62, left atrial diameter >47 mm, and complex fractionated atrial electrogram ablation are independent risk factors for AF recurrence. After PSM, the AF recurrence rate remained statistically higher in the female patients compared with the male patients.</p><p><strong>Conclusion: </strong>Compared with the male patients, the female patients were older, more symptomatic, and had worse heart function. The female patients had significantly higher AF recurrence after EIVOM combined with catheter ablation.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1556222"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Ershen Zhenwu Decoction in ameliorating chronic heart failure via JNK/MAPK-regulated apoptosis: insights from network pharmacology and experimental validation.","authors":"Yulong Liu, Xinyue Wang, Maomao Zhang, Dan Cheng, Zhenpeng Zhu, Lan Ge, Xiaoyu Cheng","doi":"10.3389/fcvm.2025.1561963","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1561963","url":null,"abstract":"<p><strong>Background: </strong>Chronic heart failure (CHF) is a complex cardiovascular disease caused by different pathological mechanisms. Modern medicine has made advancements in CHF treatment; however, there are still many challenges. Ershen Zhenwu Decoction (ESZWD) is a Xin'an medicine that has been clinically applied for years and had good efficacy against CHF; however, its underlying mechanisms remain undetermined. Therefore, this study aims to investigate the primary molecular mechanisms of ESZWD in CHF treatment and elucidate its multi-target and multi-level mode of action.</p><p><strong>Objective: </strong>The aim of this study was to investigate the main molecular mechanisms of ESZWD for the treatment of CHF and to elucidate its multi-target and multi-level mode of action.</p><p><strong>Methods: </strong>This study employed a network pharmacology approach to analyze the main ESZWD components and core targets. Furthermore, primary CHF targets were predicted to develop a protein-protein interaction (PPI) network and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Moreover, molecular docking was carried out to validate the binding between active ingredients and key targets. For <i>in vitro</i> studies, myocardial cell injury models were employed, and immunofluorescence, RT-qPCR, Western blot, and flow cytometry were carried out to validate the critical targets of relevant signaling pathways and the specific ESZWD regulatory mechanisms.</p><p><strong>Results: </strong>Network pharmacology identified 437 targets for 34 major ESZWD components. Of these, 216 drug-disease intersection targets were identified. The PPI network analysis identified the following core targets: STAT3, HSP90AA1, MAPK8, NFKB1, HIF1A, MMP9, PTGS2, BCL2L1, TLR4, and ESR1. GO analysis revealed that these targets were associated with exogenous stimuli responses, phosphorylation regulation, inflammatory response, and protein tyrosine kinase activity. Furthermore, KEGG analysis showed that ESZWD predominantly impacts cancer, inflammatory response, and apoptosis pathways, with c-Jun N-terminal kinase/mitogen-activated protein kinase (JNK/MAPK)-regulated apoptosis being a key pathway. <i>In vitro</i> analyses revealed that ESZWD effectively inhibited JNK activation, modulated MAPK signaling, downregulated pro-apoptotic gene expression, and significantly reduced cardiomyocyte apoptosis rates, thus validating the network pharmacology findings.</p><p><strong>Conclusion: </strong>Our study shows that paeoniflorin, acetylaconitine, and cryptotanshinone bind to key proteins in the JNK/MAPK apoptosis pathway. <i>In vitro</i> validation confirms drug serum from ESZWD regulates this pathway, supporting its therapeutic potential for CHF.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1561963"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of lactylation-related gene and immune microenvironment in atrial fibrillation.","authors":"Yazhe Ma, Youcheng Wang, Yuanjia Ke, Qingyan Zhao, Jie Fan, Yang Chen","doi":"10.3389/fcvm.2025.1567310","DOIUrl":"https://doi.org/10.3389/fcvm.2025.1567310","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) is a common arrhythmia associated with an increased risk of stroke, heart failure, and mortality. Immune infiltration plays a crucial role in AF pathogenesis, yet its mechanisms remain unclear. Lactylation, a novel post-translational modification, has been implicated in immune regulation, but its association with AF remains unexplored. This study aims to elucidate the relationship between lactylation and immune infiltration in AF and identify potential diagnostic biomarkers.</p><p><strong>Methods: </strong>Gene expression data from left atrial tissue samples of AF and sinus rhythm (SR) patients were obtained from the Gene Expression Omnibus (GEO) database (GSE41177, GSE79768, GSE115574, GSE2240, GSE14975, and GSE128188). Differentially expressed genes (DEGs) between AF and SR samples were identified, followed by pathway enrichment and immune infiltration analysis. Correlation analysis and WGCNA were performed to assess interactions between lactylation-related genes and immune-associated DEGs. Machine learning models, including Random Forest and Support Vector Machine (SVM), were applied to select potential AF-related diagnostic biomarkers, and validated in the animal model (beagles; <i>n</i> = 6).</p><p><strong>Results: </strong>A total of 5,648 DEGs were identified, including six lactylation-related genes (DDX39A, ARID3A, TKT, NUP50, G6PD, and VCAN). Co-expression and WGCNA analyses identified lactylation- and immune-associated gene modules in AF. Functional enrichment analysis highlighted immune-related pathways such as T cell activation and neutrophil degranulation. A five-gene diagnostic model (FOXK1, JAM3, LOC100288798, MCM4, and RCAN1) achieved high predictive accuracy (AUC = 0.969 in training, 0.907 in self-test, and 0.950, 0.760, 0.890 in independent datasets). Experimental validation confirmed the upregulated expression of these biomarkers in AF.</p><p><strong>Conclusion: </strong>This study reveals a strong association between lactylation-related genes and immune infiltration in AF, suggesting their involvement in immune remodeling. The identified five-gene signature serves as a potential diagnostic biomarker set, offering novel insights into AF pathogenesis and contributing to improved diagnosis and targeted therapeutic strategies. Future studies integrating proteomic and single-cell analyses will further clarify the role of lactylation in AF.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1567310"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}