Journal of molecular and cellular cardiology最新文献

{"title":"Catecholaminergic stress results in signs of heart failure in PP2A-PR72 overexpressor mice","authors":"Paul Pauls ,&nbsp;Larissa Fabritz ,&nbsp;Julius R. Herting ,&nbsp;Amanda Johann ,&nbsp;Jule H. König ,&nbsp;Jan S. Schulte ,&nbsp;Matthias D. Seidl ,&nbsp;Carolina E. Soppa ,&nbsp;Uwe Kirchhefer","doi":"10.1016/j.yjmcc.2025.10.003","DOIUrl":"10.1016/j.yjmcc.2025.10.003","url":null,"abstract":"<div><h3>Background</h3><div>It is unclear whether the increase in protein expression of PP2A regulatory subunit PR72 seen in human heart failure represents a primary compensatory mechanism or the final reaction to contractile decompensation. To address this question, we have explored the effects of chronic catecholaminergic stress in a transgenic (TG) mouse model with heart-specific overexpression of PR72 that exhibits hypercontractility at basal conditions.</div></div><div><h3>Methods</h3><div>Mice were treated with isoprenaline (ISO) or NaCl for 7 days using osmotic minipumps. Hearts or isolated cardiomyocytes from the animals were functionally examined.</div></div><div><h3>Results</h3><div>We could show (i) that PR72 expression is not only increased after chronic ISO stimulation but also in other different stress and insufficiency models. In TG mice, 7 days of ISO treatment led to (ii) increased hypertrophy, pulmonary edema, more fibrosis, and higher <em>ACTA1</em> gene expression compared to wild-type (WT) mice. These effects were accompanied by (iii) a decrease in myocellular contractility and prolonged relaxation. Ca²⁺ transients (iv) showed correspondingly delayed decay kinetics in TG versus WT, while (v) the reduction of L-type calcium peak current by ISO treatment was less pronounced in TG cells. The decrease in RyR2 phosphorylation in TG (vi) supports a deterioration in contractility due to chronic ISO treatment in TG.</div></div><div><h3>Conclusion</h3><div>Our results indicate that the upregulation of PP2A-PR72 in various stress and heart failure models has a long-term effect, perpetuating the molecular and functional detrimental cardiac changes, if it does not have a triggering effect.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 66-79"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling diabetes-associated metabolic stress in human multicellular cardiac microtissues","authors":"Ren Jie Phang ,&nbsp;Nan Su ,&nbsp;Anne M. Kong ,&nbsp;Shiang Y. Lim ,&nbsp;Jarmon G. Lees","doi":"10.1016/j.yjmcc.2025.10.004","DOIUrl":"10.1016/j.yjmcc.2025.10.004","url":null,"abstract":"<div><div>Type 2 diabetes is a global health crisis, closely associated with an increased risk of heart failure due to the development of diabetic cardiomyopathy. Progress in understanding the underlying mechanisms and identifying effective treatments has been limited by the lack of robust preclinical models that accurately mimic human cardiac physiology. Human induced pluripotent stem cells (iPSCs) offer the unique ability to generate large quantities of both cardiomyocytes and non-myocytes, enabling the development of advanced models for cardiovascular research. In this study, we present engineered 3D multicellular cardiac microtissues, comprising human iPSC-derived cardiomyocytes, endothelial cells, autonomic neurons, and cardiac fibroblasts, designed to provide a more physiologically relevant platform for investigating the effects of diabetogenic conditions on human heart tissue. Under diabetogenic conditions, these multicellular cardiac microtissues exhibited reduced viability, fibrotic marker expression, and prolonged systolic and diastolic phases, closely mirroring the contractile dysfunction observed in late-stage diabetic cardiomyopathy, outcomes not replicated in traditional 2D culture of cardiomyocytes or cardiomyocyte-only microtissues. Metformin treatment prevented the manifestation of diastolic dysfunction induced by diabetogenic conditions, demonstrating the utility of multicellular cardiac microtissues for drug assessment. Our findings emphasize the critical role of non-myocytes in the progression of cardiac dysfunction induced by hyperglycaemia and hyperlipidaemia, underscoring their importance in disease modelling. These iPSC-derived multicellular cardiac microtissues represent a significant advancement in preclinical models for diabetic cardiomyopathy, providing a more accurate platform for mechanistic studies and drug discovery.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 80-92"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nynrin enhances cardiac function by inhibiting mitochondrial permeability transition pore opening upon myocardial ischemia/reperfusion injury","authors":"Yuhan Wang ,&nbsp;Yujing Li ,&nbsp;Yanan Zhou ,&nbsp;Hao Zhang ,&nbsp;Jingyi Zang ,&nbsp;Chaofan Yang ,&nbsp;Zeyu Gao ,&nbsp;Yu Hou ,&nbsp;Moshi Song","doi":"10.1016/j.yjmcc.2025.10.002","DOIUrl":"10.1016/j.yjmcc.2025.10.002","url":null,"abstract":"<div><div>Acute myocardial infarction (AMI) is a leading cause of cardiovascular disease-related death. Reperfusion therapies, although essential, can exacerbate damage through myocardial ischemia/reperfusion (I/R) injury. Cyclophilin D (CypD) and mitochondrial permeability transition pore (mPTP) opening have been identified as potential therapeutic targets for I/R injury. However, clinical trials with cyclosporin A (CsA) have shown mixed results, highlighting the urgent need for alternative strategies to suppress CypD expression or activity. In this study, we explored the role of Nynrin, a newly identified transcriptional repressor of peptidylprolyl isomerase F (<em>Ppif</em>) that encodes CypD, in mitigating I/R injury by regulating mPTP opening. We first observed that <em>Nynrin</em> was downregulated in adult mouse hearts subjected to I/R and in primary adult mouse cardiomyocytes upon oxygen-glucose deprivation/reperfusion (OGD/R). Subsequently, we generated a tamoxifen-inducible cardiomyocyte-specific <em>Nynrin</em>-knockout (<em>Nynrin</em>-cKO) mouse model, which was well-tolerated in otherwise normal adult mouse hearts. Notably, <em>Nynrin</em>-cKO mice exhibited exacerbated contractile dysfunction and cardiac injury, characterized by enhanced <em>Ppif</em> transcription, CypD expression, mPTP opening, and cardiomyocyte death when subjected to I/R. Furthermore, the exacerbated I/R-induced cardiac dysfunction in <em>Nynrin</em>-cKO mice was significantly reversed by CsA, an mPTP inhibitor that targets CypD, indicating that the intensified pathological manifestations in <em>Nynrin</em>-cKO mice during I/R injury were dependent on CypD and mPTP. Conversely, Nynrin overexpression in primary adult mouse cardiomyocytes blunted <em>Ppif</em>/CypD upregulation and restrained mPTP opening, thus reducing cardiomyocyte damage upon OGD/R. Taken together, our findings highlight the critical role of Nynrin in regulating CypD and mPTP in I/R injury and suggest that targeting Nynrin may be a promising therapeutic strategy for mitigating cardiac dysfunction in managing I/R injury.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 93-103"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies","authors":"Dilip Thomas ,&nbsp;Phillip C. Yang ,&nbsp;Joseph C. Wu ,&nbsp;Nazish Sayed","doi":"10.1016/j.yjmcc.2025.09.008","DOIUrl":"10.1016/j.yjmcc.2025.09.008","url":null,"abstract":"<div><div>The COVID-19 pandemic has revealed that the impact of SARS-CoV-2 infection extends well beyond the acute phase, with long-term sequelae affecting multiple organ systems, most notably, the cardiovascular system. Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms such as fatigue, dyspnea, chest pain, and palpitations, which can last for months or even years after initial recovery. Increasing evidence implicates immune dysregulation, endothelial dysfunction, persistent viral antigens, and coagulopathy as central drivers of cardiovascular complications. Mechanistic studies demonstrate that direct viral infection of cardiac and vascular cells, along with autoantibody formation and cytokine-mediated injury, contribute to myocardial inflammation, fibrosis, and arrhythmias. Sex-based immunological differences and underlying comorbidities further influence individual susceptibility and disease trajectory. Large-scale epidemiological studies have confirmed significantly increased risks of pericarditis, cardiomyopathy, dysrhythmias, and heart failure among COVID-19 survivors. In parallel, the emergence of advanced preclinical platforms, including patient-derived induced pluripotent stem cell (iPSC)-based cardiac organoids, engineered heart tissues, and organ-on-a-chip systems has enabled mechanistic dissection of Long COVID pathophysiology. These human-relevant models, when integrated with clinical datasets and artificial intelligence (AI)-driven analytics, offer powerful tools for biomarker discovery, risk stratification, and precision therapeutic development. This review synthesizes the current understanding of cardiovascular involvement in Long COVID, highlights key mechanistic insights from both clinical and preclinical studies, and outlines future directions for diagnostic and therapeutic innovation.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 37-50"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model","authors":"Sonette Steczina ,&nbsp;Saffie Mohran ,&nbsp;Matthew C. Childers ,&nbsp;Timothy S. McMillen ,&nbsp;Ateeqa Naim ,&nbsp;Matvey Pilagov ,&nbsp;Marica Dente ,&nbsp;Kristina B. Kooiker ,&nbsp;Christian Mandrycky ,&nbsp;Khushi Tawde ,&nbsp;Jennifer Hesson ,&nbsp;Jing Zhao ,&nbsp;Julie Mathieu ,&nbsp;J. Manuel Pioner ,&nbsp;Michael A. Geeves ,&nbsp;Weikang Ma ,&nbsp;Farid Moussavi-Harami ,&nbsp;Neil M. Kad ,&nbsp;Michael Regnier","doi":"10.1016/j.yjmcc.2025.10.008","DOIUrl":"10.1016/j.yjmcc.2025.10.008","url":null,"abstract":"<div><div>The R403Q mutation in the sarcomere protein beta-myosin heavy chain (β-MHC) is a known genetic cause of hypertrophic cardiomyopathy (HCM), associated with ventricular hypercontractility, impaired relaxation, and cardiac arrhythmias. Despite extensive research, the mutations impact on myosin contractile properties remains unclear partly due to discrepancies across different model systems. In this study, we used a multidisciplinary approach to explore mutational effects using two distinct heterozygous R403Q systems: a Yucatan minipig model and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). X-ray diffraction of R403Q minipig ventricular muscle demonstrated reduced order of the thick filament, suggesting destabilization of the inhibited OFF (vs. ON) state of myosin in relaxed muscle, which correlated with elevated force at submaximal calcium. Super-resolution, single-molecule fluorescence microscopy indicated elevated ATPase activity in thick filament zones lacking cardiac myosin binding protein-C (cMyBP-C). Furthermore, R403Q myofibrils exhibited slower activation and relaxation kinetics, with reduced sensitivity to ADP. Molecular dynamics simulations suggested that altered interactions at the actomyosin interface contribute to these effects, rather than changes at the nucleotide binding pocket, typically associated with ADP release. Human engineered heterozygous R403Q hiPSC-CMs exhibited reduced maximal myofibril force, slowed relaxation kinetics, and hypercontraction in engineered heart tissue constructs-consistent with HCM phenotypes observed in the heterozygous porcine model. Our results demonstrate that the R403Q mutation induces contractile dysfunction within the early stages of stem cell derived cardiomyocyte development and in juvenile minipigs, and that hypercontractility and slower contractile kinetics may result from a combination of an increased population of activated (ON) myosin heads and delayed detachment during cross-bridge cycling, respectively.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 143-160"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting gut microbiotasu-derived butyrate for Ferroptosis inhibition in Sepsis-induced myocardial dysfunction","authors":"Jianfei Xiong ,&nbsp;Guoxiang Liu ,&nbsp;Tianyuan Jia ,&nbsp;Qian Yang ,&nbsp;Changqing Zhu ,&nbsp;Shiwei Wang","doi":"10.1016/j.yjmcc.2025.10.005","DOIUrl":"10.1016/j.yjmcc.2025.10.005","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced myocardial dysfunction (SIMD) is a critical complication of sepsis, and ferroptosis has been identified as a key contributor to its pathogenesis. Emerging evidence suggests that sepsis profoundly disrupts the gut microbiota composition, leading to dysbiosis. Butyrate, a short-chain fatty acid produced by gut microbiota, has been implicated in ferroptosis regulation; however, its role in SIMD remains controversial. This study aims to elucidate the protective effects of gut microbiota-derived butyrate against SIMD through ferroptosis modulation.</div></div><div><h3>Methods</h3><div>This study assessed cardiac function using echocardiography and quantified myocardial injury biomarkers via ELISA. Myocardial iron deposition was evaluated using Prussian blue staining. The gut microbiota composition was analyzed using 16S rRNA gene sequencing. Ferroptosis-related protein expression in SIMD heart tissues and H9C2 cardiomyocytes was examined via western blotting to determine the regulatory role of butyrate.</div></div><div><h3>Results</h3><div>Sepsis-induced gut microbiota dysbiosis was characterized by a significant reduction in butyrate-producing bacteria. Echocardiographic assessments (CO, EF), myocardial injury markers (BNP, cTnI), histopathological analysis (H&amp;E staining), and cardiomyocyte ultrastructure (TEM) demonstrated that butyrate administration significantly alleviated myocardial injury in SIMD. Mechanistically, butyrate mitigated oxidative stress by increasing GSH levels and reducing MDA levels. Furthermore, butyrate treatment reversed the sepsis-induced downregulation of GPX4 and suppressed the upregulation of ACSL4 and PTGS2, thereby inhibiting ferroptosis.</div></div><div><h3>Conclusion</h3><div>These findings highlight the protective role of butyrate in SIMD, with ferroptosis inhibition serving as a key cardioprotective mechanism. Targeting gut microbiota-derived butyrate may represent a promising therapeutic strategy for sepsis-induced myocardial injury.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 119-127"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the NLRP3 Inflammasome-Gasdermin D Axis to Combat Cardiovascular Diseases","authors":"Judy S. Choi ,&nbsp;Mehnaz Pervin ,&nbsp;James E. Vince ,&nbsp;Arpeeta Sharma ,&nbsp;Judy B. de Haan","doi":"10.1016/j.yjmcc.2025.09.006","DOIUrl":"10.1016/j.yjmcc.2025.09.006","url":null,"abstract":"<div><div>Cardiovascular disease remains a leading global cause of mortality, with inflammation playing a crucial role in driving its pathology. Despite advancements in cardiovascular disease management, current treatment options primarily address risk factors and symptoms rather than underlying disease mechanisms. Among the key mechanistic drivers are the NLRP3 multiprotein inflammasome complexes of the innate immune system, which are activated in response to cellular stress or injury. One of the key downstream effectors of NLRP3 activation is gasdermin D, which forms pores in the plasma membrane to initiate pyroptotic cell death, leading to the release of pro-inflammatory cytokines. This review will highlight the role of NLRP3 inflammasome activation and gasdermin D-mediated pyroptosis in driving cardiovascular diseases, including atherosclerosis, myocardial infarction, ischemic stroke and diabetic cardiomyopathy. It will also identify recent innovative therapeutic approaches that target the NLRP3 inflammasome-gasdermin D axis, which are currently being evaluated in preclinical studies and clinical trials.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 1-14"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 mediates iron overload and ferroptosis via transcriptional regulation of TfR1 in PM2.5-exposed cardiomyocytes","authors":"Xiaosu Yuan ,&nbsp;Lin Song ,&nbsp;Peiyan Wang ,&nbsp;Dandan Xiao ,&nbsp;Yi Jia ,&nbsp;Lin Ye ,&nbsp;Kangwei Jia ,&nbsp;Jianxun Wang ,&nbsp;Wei Ding","doi":"10.1016/j.yjmcc.2025.10.007","DOIUrl":"10.1016/j.yjmcc.2025.10.007","url":null,"abstract":"<div><div>As air pollution intensifies, the health risks associated with PM2.5 have gained increasing global attention. Previous research has established a link between PM2.5 exposure and increased risk of cardiovascular diseases (CVDs), yet the underlying mechanisms remain unclear. In this study, we demonstrate that PM2.5 induces ferroptosis in myocardial cells both in vitro and in vivo. We also show that PM2.5 exposure increases lipid peroxidation levels and cellular iron content while depleting glutathione (GSH). Notable alterations in the expression of transferrin receptor protein 1 (TfR1), ferritin light chain (FTL), and ferritin heavy chain (FTH) suggest that the dysfunction in iron uptake and storage plays a pivotal role in ferroptosis. Moreover, we observed that PM2.5 exposure upregulates p53 expression, which transcriptionally regulates TfR1 synthesis. This leads to increased iron influx into cells, causing iron overload and ultimately contributing to ferroptosis and myocardial injury. In conclusion, our findings suggest that PM2.5 promotes ferroptosis in the myocardium via the p53/TfR1 pathway.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 128-142"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial effects of aryl hydrocarbon receptor activation on post-infarction myocardial metabolism, inflammation and fibrosis: implications from multi-omics","authors":"Yong Chu ,&nbsp;Jiang Zhu ,&nbsp;Shuaijie Chen ,&nbsp;Xiaoyan Lin ,&nbsp;Zhongxing Zhou ,&nbsp;Ruming Shen ,&nbsp;Hongzhuang Wang ,&nbsp;Longqing Chen ,&nbsp;Jinxiu Lin ,&nbsp;Hailin Zhang ,&nbsp;Dajun Chai","doi":"10.1016/j.yjmcc.2025.10.006","DOIUrl":"10.1016/j.yjmcc.2025.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Post-infarction metabolism changes, inflammatory responses, and fibrosis are crucial contributors to adverse cardiac remodeling. 2-(1′H-indole-3′‑carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), the aryl hydrocarbon receptor (AHR) ligand, has demonstrated effective AHR activation, yet its impact and mechanisms in myocardial infarction (MI) remain unclear.</div></div><div><h3>Methods</h3><div>The MI model was established by ligating left anterior coronary artery, and ITE was administered for 4 weeks. Echocardiography and hemodynamic monitoring were used to assess cardiac structure and function. Hematoxylin-eosin and Masson's trichrome were used to examine morphology and collagen deposition. Transmission electron microscopy was employed to examine mitochondrial morphology. The transcriptome and metabolome were used to screen for key targets and pathways. Hypoxic neonatal rat cardiomyocytes and fibroblasts models combined with adenoviral AHR knockdown were used to verify key targets and pathways.</div></div><div><h3>Results</h3><div>ITE intervention significantly improved cardiac structure and function, mitochondrial morphology, fibrosis and inflammation in MI rats. Multi-omics revealed that differentially expressed genes and metabolites were enriched in glucose metabolism related pathways and identified a key target, HK2. Compared to MI group, ITE significantly improved the expression of key enzymes in glucose metabolism after MI. In vitro, AHR activation by ITE and tapinarof significantly ameliorated hypoxia-induced abnormalities in HK2, CISY, OGDH, fibrosis, and inflammatory markers, while hexokinase inhibitor eliminated the beneficial effects of ITE. Moreover, AHR knockdown impairs glucose metabolism and promotes inflammation and fibrosis.</div></div><div><h3>Conclusion</h3><div>The AHR activation by ITE mitigates inflammation and fibrosis, improves cardiac structure and function by promoting HK2 and glucose metabolism after MI.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 104-118"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast metabolic reprogramming determines scar quality and sex-specific remodeling after infarction","authors":"Xinyu Nie ,&nbsp;Xingyue Feng ,&nbsp;Can Xu","doi":"10.1016/j.yjmcc.2025.10.010","DOIUrl":"10.1016/j.yjmcc.2025.10.010","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"209 ","pages":"Pages 161-162"},"PeriodicalIF":4.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145474494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}