Circulation research最新文献

{"title":"Acetyltransferase MOF Regulates Macrophage Inflammation in Abdominal Aortic Aneurysms","authors":"Xiaobing He,Nicholas Juriga,Sama Salih,Brennan Callow,Dominique Pierre-Louis,Amrita Joshi,Rachael Bogle,Lam C. Tsoi,Andrea Obi,Johann E. Gudjonsson,Katherine Gallagher,Frank M. Davis","doi":"10.1161/circresaha.126.329212","DOIUrl":"https://doi.org/10.1161/circresaha.126.329212","url":null,"abstract":"BACKGROUND: Abdominal aortic aneurysms (AAAs) are a life-threatening cardiovascular disease for which there is a lack of therapy preventing aortic rupture. During AAA formation, pathological vascular remodeling is driven by an imbalance of proinflammatory and anti-inflammatory macrophage responses, and mechanisms regulating macrophage-mediated inflammation remain undefined. Recent evidence suggests that males absent on the first (MOF), a histone acetyltransferase, can play a critical role in establishing macrophage phenotype and modulating innate immune response. METHODS: Single-cell RNA sequencing analysis of human AAAs and control tissues was performed to analyze MOF expression in aortic monocyte/macrophages and the inflammatory immune response. Mice underwent 2 murine AAA models: either Ang II (angiotensin II) or topical porcine pancreatic elastase. To investigate the role of MOF in AAA development, targeted inhibition was performed with MG-149 administration or in mice genetically deficient in macrophage-specific MOF ( Mof f/f Lyz2 Cre+ ). Finally, flow cytometry and chromatin immunoprecipitation were conducted to analyze macrophage phenotype and levels of histone (H) lysine (K) acetylation (H4K16ac) in human and murine AAA macrophages. RESULTS: Using single-cell RNA sequencing of human AAA tissues and multiple murine AAA models, we identified that MOF is increased in aortic monocyte/macrophages associated with upregulation of inflammatory transcriptional programs. Mechanistically, TNF-α signaling promotes the induction of MOF, which in turn induces NF-κB–mediated inflammatory gene transcription by increasing the activating H4K16ac mark on gene promoters in infiltrating aortic macrophages. In vivo targeted inhibition of the MOF pathway, with myeloid-specific genetic depletion ( Mof f/f Lyz2 Cre+ ) or pharmacological inhibition in the elastase- and angiotensin II–induced AAA model, preserved macrophage function, decreased elastin fragmentation, attenuated aortic inflammation, and markedly reduced AAA development. CONCLUSIONS: Our study provides important evidence that MOF regulates macrophage phenotypic function and inflammation during human and murine AAA development. Targeting the MOF pathway affords the opportunity to prevent pathological macrophage infiltration within the aortic wall and potentially limit AAA development.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"175 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGFR1/KLB-MFG-E8 Maintains Microvascular Integrity and Adaptive Cardiac Remodeling.","authors":"Sanskruti R Gare, Nasser H Alatawi, Xinyi Chen, Jiayan Zhang, Claire Ross, Oveena Fonseka, Yihua Han, Namrita Kaur, Andrea Ruiz-Velasco, Xiangjun Zhao, Yingjuan Liu, Riham R E Abouleisa, Susanne S Hille, Tao Wang, Sabu Abraham, Bernard D Keavney, Martin K Rutter, Elizabeth J Cartwright, Gareth Howell, Tamer M A Mohamed, Oliver J Müller, Wei Liu","doi":"10.1161/CIRCRESAHA.125.327950","DOIUrl":"10.1161/CIRCRESAHA.125.327950","url":null,"abstract":"<p><strong>Background: </strong>Endothelial defects in the heart are a contributor to cardiac pathological remodeling and dysfunction, which can be influenced by cardiomyocytes. Here, we explore cardioprotective crosstalk between cardiomyocytes and endothelial cells under diabetic conditions.</p><p><strong>Methods: </strong>Type 2 diabetes was induced in male and female mice using a high-fat, high-sucrose diet in conjunction with low-dose streptozotocin. Cardiomyocyte-specific deletion of FGFR1 (fibroblast growth factor receptor 1) or KLB (beta-Klotho) was achieved by crossing floxed mice with αMHC (alpha-myosin heavy chain)-Cre transgenic mice, while the treatment potential was assessed by recombinant adeno-associated virus 9 delivery systems or administration of recombinant protein. Various in vitro models were used to investigate the mechanisms under a diabetes-like condition. The molecular mechanisms were explored through transcriptomics, proteomics, cytokine arrays, angiogenesis assays, histology, and luciferase reporter assays.</p><p><strong>Results: </strong>Human diabetic hearts exhibited impaired angiogenic pathways with a marked reduction in myocardial capillary density. Multiomics profiling also revealed alterations in the FGFR1 (fibroblast growth factor receptor 1) pathway in mouse diabetic hearts. Both cardiomyocyte-specific FGFR1- and KLB- knockout mice exhibited reduced capillary abundance and developed decompensated cardiac remodeling. Mechanistic studies identified CEBPβ (CCAAT/enhancer binding protein beta) as a downstream transcription factor of the FGFR1/KLB pathway regulating MFG-E8 (milk fat globule-EGF factor 8) expression in cardiomyocytes. Cardiomyocyte-secreted MFG-E8 enhanced endothelial viability and branching. Importantly, the detrimental effects on the heart were rescued by corestoration of cardiac FGFR1 and KLB, whereas neither alone was sufficient, underscoring their synergistic action against diabetic stress. Finally, genetic or pharmacological enhancement of MFG-E8 reversed myocardial capillary rarefaction and led to an improvement in cardiac function, albeit with more pronounced therapeutic effects in males.</p><p><strong>Conclusions: </strong>Our findings demonstrate FGFR1/KLB-mediated cardioprotective mechanisms through cardiomyocyte-endothelial cell crosstalk and provide evidence that preserving adaptive remodeling represents a promising strategy to alleviate heart failure in both sexes.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral KCl Supplementation Safely Reduces Body Na⁺ Surplus and Blood Pressure.","authors":"Adriana Marton, Hieu T N Tran, Norihiko Morisawa, Ismail Osman, Seyed Ehsan Saffari, Tzy Tiing Lim, Wan Keat Yam, Matthew B Chuah, Wei Lin Tay, Wai Lun Moy, Pek-Lan Khong, Calvin W L Chin, Armin M Nagel, Roger S Y Foo, Friedrich C Luft, Eric Finkelstein, Jean-Paul Kovalik, Manfred Rauh, Troy Puar, Jens Titze","doi":"10.1161/CIRCRESAHA.126.329131","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329131","url":null,"abstract":"<p><strong>Background: </strong>Potassium-enriched table salt lowers blood pressure (BP) and reduces cardiovascular mortality. Whether these beneficial effects stem from reduced Na⁺ intake, increased K⁺ intake, or both is unknown. We tested the hypothesis that oral potassium chloride (KCl) supplementation lowers body Na⁺ content and BP in patients with essential hypertension (EH) or hyperaldosteronism, independent of salt intake.</p><p><strong>Methods: </strong>Between February 2024 and February 2025, we conducted a single-arm, prospective, longitudinal study with nonrandomized oral KCl intervention in 40 participants with hypertension. All received personalized (blood K⁺-adjusted) KCl supplementation (Span-K tablets) for 6 to 9 weeks. After the intervention, participants completed a routine diagnostic workup and were classified with EH or hyperaldosteronism. Primary end point: baseline muscle Na⁺ surplus in hyperaldosteronism. Secondary end point: interventional muscle Na⁺ mobilization and BP reduction.</p><p><strong>Results: </strong>Seventeen participants were diagnosed with EH, and 23 with hyperaldosteronism. At baseline, patients with hyperaldosteronism showed higher muscle Na⁺ content (24.67±2.93 versus 22.48±3.37 mmol/L tissue volume, <i>P</i>=0.023; primary end point). Oral KCl increased 24-hour urine K⁺ excretion without altering 24-hour urine Na⁺. KCl supplementation successfully eliminated the muscle Na⁺ surplus in the hyperaldosteronism group (-1.90 mmol/L tissue volume [CI, -3.20 to -0.60]; <i>P</i>=0.005; secondary end point), lowered blood Na⁺/K⁺ ratios in both groups (EH, -5.34 [CI, -7.69 to -2.99]; <i>P</i>=4.6×10^-5; hyperaldosteronism, -7.02 [CI, -9.04 to -5.01]; <i>P</i>=2.1×10^-8), and reduced systolic BP (EH, -8.33 mm Hg [CI, -14.55 to -2.12]; <i>P</i>=0.010; hyperaldosteronism, -7.35 mm Hg [CI, -12.69 to -2.01]; <i>P</i>=0.008). To account for early study termination, a conservative significance threshold of α=0.025 was implemented, which all end points crossed.</p><p><strong>Conclusions: </strong>Oral KCl supplementation mobilizes intracellular Na⁺ stores, corrects pathological Na⁺/K⁺ distribution, and lowers BP across hypertension phenotypes. This safe, targeted approach warrants consideration as a scalable public health strategy for cardiovascular disease prevention.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT06569589.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective cGAS Inhibition Is Cardioprotective After Myocardial Infarction.","authors":"Van K Ninh, Kelly A Pike, Betul B Gunes, Gilda Castellanos, Bo Zhang, Samuel Gaudreault, Zhenxing Fu, Michael A Crackower, Kevin R King","doi":"10.1161/CIRCRESAHA.126.328581","DOIUrl":"10.1161/CIRCRESAHA.126.328581","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e328581"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria Take Up and Dispose of Cytosolic Protein Aggregates.","authors":"Eun-Ah Sung, Junichi Sadoshima","doi":"10.1161/CIRCRESAHA.126.329602","DOIUrl":"10.1161/CIRCRESAHA.126.329602","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 8","pages":"e329602"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desmosome-to-Sarcomere Mechanosignaling in Desmoplakin Cardiomyopathy.","authors":"Maria Florencia Racioppi, Martin Vila Petroff","doi":"10.1161/CIRCRESAHA.126.329363","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329363","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 8","pages":"e329363"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Molecule Imaging Reveals ERK-Dependent Spatial Translation in Cardiomyocytes.","authors":"Itai Erlich, Guy Douvdevany, Rami Haddad, Benjamin L Prosser, Izhak Kehat","doi":"10.1161/CIRCRESAHA.126.329033","DOIUrl":"10.1161/CIRCRESAHA.126.329033","url":null,"abstract":"<p><strong>Background: </strong>Translational control of gene expression is crucial in cardiomyocytes, particularly in response to hypertrophic stimuli. The ERK (extracellular signal-regulated kinase) pathway plays a key role in inducing cardiac hypertrophy and regulating specific protein translation. However, it remains unclear how this specificity is achieved, and the spatiotemporal regulation of protein translation is not fully understood.</p><p><strong>Methods: </strong>We used SINAP (single-molecule imaging of nascent peptide) reporters to visualize and analyze the translation dynamics in single adult rat ventricular cardiomyocytes and tracked active translation sites at high spatiotemporal resolution. We also examined the effects of adrenergic stimulation and the role of the ERK pathway in translation localization.</p><p><strong>Results: </strong>Our findings revealed that translation sites are primarily localized near Z-lines in cardiomyocytes, with some sites being highly dynamic and moving during translation. The 3' untranslated regions did not significantly change the localization of translation. Many translation sites colocalized with microtubules, and their movement predominantly occurred along microtubular tracks. Adrenergic stimulation led to a transient shift in translation activity toward the perinuclear region, peaking at 12 hours and requiring ERK pathway activity for this localization change. This shift is part of the hypertrophic response and is required for early translation of genes such as <i>Nppa</i>.</p><p><strong>Conclusions: </strong>Our high-resolution single-cell study demonstrates that protein translation in cardiomyocytes is dynamic and responsive to hypertrophic stimuli in an ERK-dependent manner. The localized translation mechanism allows cardiomyocytes to rapidly adapt to changing environments by preferentially translating mRNAs in the perinuclear region. These findings provide new insights into the spatial regulation of translation in cardiomyocytes and its role in cardiac hypertrophy.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e329033"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FAP-Directed CAR-NKT Cells for Multi-Target Suppression of Atherosclerotic Progression.","authors":"Enbo Zhu, Yan-Ruide Li, Jae Min Cho, Robert Kropp, Yunpei Zhang, Yas Sanaiha, Oh Jin Kwon, Yichen Zhu, Seul-Ki Park, Brian Arianpour, Melissa Justo, Peng Zhao, Shaolei Wang, Mingxia Gu, Peyman Benharash, Lili Yang, Tzung K Hsiai","doi":"10.1161/CIRCRESAHA.126.328898","DOIUrl":"10.1161/CIRCRESAHA.126.328898","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e328898"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulated HSPG Signaling Directs Epicardial Behavior to Support Cardiac Formation.","authors":"Andia N Redpath, Irina-Elena Lupu, Louis Haffreingue, Quang M Dang, Ian R McCracken, Tamara Carsana, Toin H van Kuppevelt, Joaquim Miguel Vieira, Nicola Smart","doi":"10.1161/CIRCRESAHA.125.327330","DOIUrl":"10.1161/CIRCRESAHA.125.327330","url":null,"abstract":"<p><strong>Background: </strong>Pathways controlling cardiac cell behavior share a common dependency on heparan sulfate proteoglycans (HSPGs), which tightly regulate signaling at extracellular locations. This signaling is essential for cardiac development, yet how HSPGs are regulated in the forming heart is unknown. The epicardium is a rich source of HSPG-dependent signaling and cellular progenitors. We hypothesized that extracellular heparan sulfate modifiers, 6-<i>O</i>-endosulfatases, orchestrate progenitor cell behavior to support cardiogenesis.</p><p><strong>Methods: </strong>We used single-cell RNA sequencing, microscopy, and flow cytometry-based single-molecule RNA in situ hybridization (ISH) to systematically profile 6-<i>O</i>-endosulfatases and target HSPGs in the embryonic mouse heart. Subsequently, we utilized knockout and knockdown models that identified gene associations and a role for the main epicardial 6-<i>O</i>-endosulfatase isoform, <i>Sulfatase (Sulf)1</i>. Transcriptional regulation of <i>Sulf1</i> was assessed using assay for transposase-accessible chromatin (ATAC) and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) with sequencing, luciferase assays, and siRNA, and the impact on epicardial cell behavior was confirmed in vivo and using in vitro functional assays.</p><p><strong>Results: </strong>Despite identical function, we find that <i>Sulf1</i> is expressed in the embryonic epicardium, while <i>Sulfatase (Sulf)2</i> is expressed broadly throughout the myocardium. We show that epicardial SULF1 dynamically regulates HSPG sulfation to fine-tune the magnitude and duration of signaling to impact cell fate and cardiac morphogenesis. Single-cell genomics and lineage tracing studies reveal <i>Sulf1</i> to be strongly coexpressed with key transcriptional regulator <i>Wt1</i> (Wilms tumor 1) in the epicardium, with reduction of both coinciding with epithelial-to-mesenchymal transition and quiescence. CUT&RUN-seq revealed transcriptional control of <i>Sulf1</i> by WT1, which directly impacts essential HSPG-dependent downstream signaling. Ligand-receptor interaction predictions and functional assays indicated that FGF (fibroblast growth factor)-2 and TGF-β (transforming growth factor β)-driven processes were governed by this regulatory interaction.</p><p><strong>Conclusions: </strong>Our study highlights, for the first time, essential fine-tuning of HSPG-dependent signaling to modulate key processes in heart formation, offering potential insights for therapeutically targeting congenital heart disease and enhancing epicardial proregenerative behaviors.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e327330"},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reducing Nuclear Rupture Rescues Gene Expression and Survival in <i>LMNA</i>-DCM.","authors":"Noam Zuela-Sopilniak, Julien L P Morival, Ioannis Ntekas, Margaret A Elpers, Rohit Agarwal, Sarah J Henretta, Jacob D Odell, Iwijn De Vlaminck, Jan Lammerding","doi":"10.1161/CIRCRESAHA.125.327744","DOIUrl":"10.1161/CIRCRESAHA.125.327744","url":null,"abstract":"<p><strong>Background: </strong>Mutations in the <i>LMNA</i> gene, which encodes the nuclear envelope proteins lamins A and C, account for 6% to 8% of all cases of congenital dilated cardiomyopathy. <i>LMNA</i>-related dilated cardiomyopathy is among the most severe forms of dilated cardiomyopathy, with limited treatment options due to an incomplete understanding of its molecular mechanisms.</p><p><strong>Methods: </strong>We generated an inducible, cardiomyocyte-specific <i>Lmna</i> deletion mouse model (cKO) and conducted comprehensive bulk, single-nucleus, and spatial transcriptomic analyses on left ventricular free wall tissue from cKO and controls lacking the floxed <i>Lmna</i> alleles mice across disease progression. Concurrent cardiomyocyte-specific expression of a dominant-negative KASH domain protein (DN KASH) that disrupts the linker of nucleoskeleton and cytoskeleton complex was used to determine the role of mechanically induced nuclear envelope rupture in altered gene expression.</p><p><strong>Results: </strong>We identified genes misregulated early in disease that were enriched for cytosolic pattern recognition receptor signaling and innate immunity. These transcriptional changes were primarily driven by a subset of disease-specific cardiomyocytes. Spatial and single-nucleus transcriptomics revealed aberrant interactions between these cardiomyocytes, fibroblasts, and immune cells, contributing to widespread transcriptional dysregulation in cKO hearts. Concurrent disruption of the linker of nucleoskeleton and cytoskeleton complex significantly reduced nuclear envelope rupture, normalized expression of over half the dysregulated genes, and dramatically improved cardiac function and survival in cKO mice.</p><p><strong>Conclusions: </strong>Our findings support a model in which nuclear envelope rupture in cKO cardiomyocytes triggers cytosolic DNA sensing pathways and maladaptive cell-cell communication with fibroblasts and immune cells, driving inflammation, fibrosis, and cardiac dysfunction. The work presented here points to novel strategies for treating <i>LMNA</i>-dilated cardiomyopathy.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":""},"PeriodicalIF":18.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}