Journal of molecular and cellular cardiology最新文献

{"title":"Endothelial SHP-1 regulates diabetes-induced abnormal collateral vessel formation and endothelial cell senescence","authors":"Alexandre Nadeau ,&nbsp;Marike Ouellet ,&nbsp;Raphaël Béland ,&nbsp;Clément Mercier ,&nbsp;Stéphanie Robillard ,&nbsp;Farah Lizotte ,&nbsp;Marc-Antoine Despatis ,&nbsp;C. Florian Bentzinger ,&nbsp;Pedro Geraldes","doi":"10.1016/j.yjmcc.2025.03.005","DOIUrl":"10.1016/j.yjmcc.2025.03.005","url":null,"abstract":"<div><h3>Background</h3><div>Critical limb ischemia is a major cause of peripheral arterial disease and morbidity affecting patients with diabetes. Diabetes-induced premature senescence of endothelial cells (EC) has been proposed as a mechanism leading to impaired ischemia-driven angiogenesis. We showed that hyperglycemia induced expression of the protein tyrosine phosphatase SHP-1, which reduced angiogenic factor activity in ischemic muscle of diabetic mice. Here, we evaluate the impact of SHP-1 deletion on EC function and senescence.</div></div><div><h3>Methods</h3><div>Ligation of the femoral artery was performed in nondiabetic (NDM) and 3 months diabetic (DM) mice with EC-specific deletion of SHP-1. Cell migration, proliferation and protein expression were evaluated in EC exposed to normal (NG) or high glucose (HG) concentrations. Gastrocnemius and tibial artery of patients with diabetes were collected and analyzed.</div></div><div><h3>Results</h3><div>Blood flow reperfusion and limb function were reduced by 43 % and 82 %, respectively in DM mice as compared to NDM mice. EC-specific deletion of SHP-1 in DM mice restored blood flow reperfusion by 60 %, and limb function by 86 %, while capillary density was similar to NDM mice. Moreover, ablation of SHP-1 in EC prevented diabetes-induced expression of the senescence markers p53 and p21 and counteracted Nrf2 downregulation. In EC, elevated expression of beta-galactosidase, p21 and p53, and suppression of Nrf2 and VEGF actions were observed in EC exposed to HG levels and human muscle and artery of patients with diabetes, effects that were reversed by overexpression of dominant negative SHP-1.</div></div><div><h3>Conclusion</h3><div>SHP-1 in EC is a central effector of diabetes-induced senescence and induces aberrant collateral vessel formation and blood flow reperfusion. Reduced SHP-1 expression counteracts these pathologic features.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"202 ","pages":"Pages 50-63"},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605203","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":"Ca2+ sensitivity changes in skinned myocardial fibers induced by myosin–actin crossbridge-independent sarcomere stretch: Role of N-domain of MyBP-C","authors":"Xutu Wang ,&nbsp;Nathan Kallish ,&nbsp;R. John Solaro ,&nbsp;Wen-Ji Dong","doi":"10.1016/j.yjmcc.2025.03.004","DOIUrl":"10.1016/j.yjmcc.2025.03.004","url":null,"abstract":"<div><div>Sarcomere length-dependent activation (LDA) is the key cellular mechanism underlying the Frank-Starling law of the heart, in which sarcomere stretch leads to increased Ca²⁺ sensitivity of myofilament and force of contraction. Despite its key role in both normal and pathological states, the precise mechanisms underlying LDA remain unclear but are thought to involve multiple interactions among sarcomere proteins, including troponin of the thin filament, myosin, titin and myosin binding protein C (MyBP-C). Our previous study with permeabilized rat cardiac fibers demonstrated that the mechanism underlying the increase in Ca²⁺ sensitivity of thin filament induced by sarcomere stretch may involve sarcomere length (SL)-induced interactions between troponin and weakly bound, disordered relaxed state (DRX) myosin heads in diastole, rather than strong myosin–actin crossbridge interactions. In this study we investigated the role of the N-domains of MyBP-C in this newly discovered mechanism. To examine the potential role of the N-domain of MyBP-C in SL-induced myosin-troponin interactions, skinned myocardial fibers from a transgenic ΔN-MyBP-C rat with deleted N-terminal C0-C2 domains and a non-transgenic rat were reconstituted with troponin containing wild-type cTnT, cTnC(13C/51C)_AEDANS-DDPM and mutant ΔSP-cTnI or wild-type cTnI. Because the switching peptide (SP) of ΔS-cTnI is replaced by a nonfunctional peptide linker, force-generating actin-myosin crossbridge interactions of the reconstituted skinned fibers with mutant ΔSP-cTnI are inhibited regardless of the presence of Ca²⁺. This approach allowed us to examine the sensitivity of troponin/thin filament to Ca²⁺ binding in response to sarcomere stretch by monitoring Ca²⁺-induced changes in fluorescence resonance energy transfer (FRET) between AEDANS and DDPM attached to the N-domain of cTnC in the presence/absence of myosin–actin crossbridge interaction with or without deletion of C0-C2 domains of MyBP-C. Our measurements of SL-induced changes in muscle fiber mechanics and FRET Ca²⁺ sensitivities provide strong evidence that both the weakly bound myosin heads and the N-terminus of MyBP-C are critical for SL to activate troponin in the diastolic state. A model based on the results is proposed for the mechanism underlying LDA of myofilament.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"202 ","pages":"Pages 24-34"},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143592457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL7B-induced histone lactylation prevents heart failure by ameliorating cardiac remodelling","authors":"Ziqi Chen ,&nbsp;Meijun Zhong ,&nbsp;Yuhui Lin,&nbsp;Wei Zhang,&nbsp;Yinghong Zhu,&nbsp;Lin Chen,&nbsp;Ziyao Huang,&nbsp;Kaiyuan Luo,&nbsp;Zhifeng Lu,&nbsp;Zhaoqi Huang,&nbsp;Yi Yan","doi":"10.1016/j.yjmcc.2025.03.006","DOIUrl":"10.1016/j.yjmcc.2025.03.006","url":null,"abstract":"<div><h3>Introduction</h3><div>Lactylation is important for a variety of biological activities. It is reported that Class I histone deacetylases (HDAC1–3) are histone lysine delactylases. However, the role of lactylation in cardiac remodelling remains uncertain.</div></div><div><h3>Objectives</h3><div>To explore a novel regulator of lactylation and elucidate their functional mechanisms in cardiac remodelling and heart failure.</div></div><div><h3>Methods</h3><div>GSE36961, GSE141910 and GSE174691 related to HCM (hypertrophic cardiomyopathy) were separately acquired from Gene expression Omnibus. Candidate genes related to both HCM and histone lactylation were determined by the intersection of DEGs (differentially expressed genes) and module genes sifted by WGCNA (Weighted Gene Co-Expression Network Analysis). METTL7B was screened out and its expression in hypertrophic myocardium was measured by qRT-PCR and western blotting. Furthermore, immunofluorescence, immunoprecipitation, and RNA pull-down assays were utilized to identify the biological functions of METTL7B. The myocardial biopsy of HCM and transverse aortic constriction (TAC) mouse model were performed to analyze the effects of METTL7B on cardiac remodelling in vivo.</div></div><div><h3>Results</h3><div>We observed that the expression of METTL7B was down-regulated in hypertrophic myocardium, and the lactylation level was increased during the early stage and falling rapidly in the process of cardiac remodelling. Furthermore, we demonstrated that sodium lactate (NALA) administration fulfil a protective role on cardiac remodelling, and METTL7B alleviates cardiac remodelling and improves heart function by maintaining the activation of histone lactylation possibly at the later stage. Impressively, METTL7B suppressed the expression of USP38 via m6A dependent mRNA degradation, resulting in increasing ubiquitylation of HDAC3, which is a proven histone lysine delactylases.</div></div><div><h3>Conclusion</h3><div>We identifed METTL7B as a potential therapeutic target for myocardial remodelling and showed that it played a critical role in the promotion of myocardial lactylation, which is beneficial for improvement of cardiac function and attenuation of cardiac remodelling.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"202 ","pages":"Pages 64-80"},"PeriodicalIF":4.9,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A short history of the atrial NLRP3 inflammasome and its distinct role in atrial fibrillation","authors":"Theresa Poppenborg ,&nbsp;Arnela Saljic ,&nbsp;Florian Bruns ,&nbsp;Issam Abu-Taha ,&nbsp;Dobromir Dobrev ,&nbsp;Anke C. Fender","doi":"10.1016/j.yjmcc.2025.02.011","DOIUrl":"10.1016/j.yjmcc.2025.02.011","url":null,"abstract":"<div><div>Inflammasomes are multiprotein complexes of the innate immune system that mediate inflammatory responses to infection and to local and systemic stress and tissue injury. The principal function is to facilitate caspase-1 auto-activation and subsequently maturation and release of the effectors interleukin (IL)-1β and IL-18. The atrial-specific NLRP3 inflammasome is a unifying causal feature of atrial fibrillation (AF) development, progression and recurrence after ablation. Many AF-associated risk factors and co-morbidities converge mechanistically on the activation of this central inflammatory signaling platform. This review presents the historical conceptual development of a distinct atrial inflammasome and its potential causal involvement in AF. We follow the early observations linking systemic and local inflammation with AF, to the emergence of an atrial-intrinsic NLRP3 inflammasome operating within not just immune cells but also in resident atrial fibroblasts and cardiomyocytes. We outline the key developments in understanding how the atrial NLRP3 inflammasome and its effector IL-1β contribute causally to cellular and tissue-level arrhythmogenesis in different pathological settings, and outline candidate therapeutic concepts verified in preclinical models of atrial cardiomyopathy and AF.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"202 ","pages":"Pages 13-23"},"PeriodicalIF":4.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncoupling protein 3 protects against pathological cardiac hypertrophy via downregulation of aspartate","authors":"Yajun Wang ,&nbsp;Jiliang Tan ,&nbsp;Luxiao Li ,&nbsp;Shenyan Liu ,&nbsp;Xuxia Li ,&nbsp;Huitong Shan ,&nbsp;Huiyong Yin ,&nbsp;Huang-Tian Yang","doi":"10.1016/j.yjmcc.2025.03.001","DOIUrl":"10.1016/j.yjmcc.2025.03.001","url":null,"abstract":"<div><div>Metabolic remodeling involving alterations in the substrate utilization is a key feature of cardiac hypertrophy. However, the molecular mechanisms underlying regulation of tricarboxylic acid cycle intermediates by mitochondrial membrane proteins during cardiac hypertrophy have not yet been fully clarified. Mitochondrial uncoupling protein 3 (UCP3), an anion transporter located on the inner mitochondrial membrane, exerts cardioprotective effects against ischemia/reperfusion injury and its insufficiency exacerbates left ventricular (LV) diastolic dysfunction during hypertension. However, its role in pressure overload-induced cardiac hypertrophy remains unknown. Here, we found that UCP3 was downregulated in the mouse LV with transverse aortic constriction (TAC)-induced pathological hypertrophy and in phenylephrine (PE)-stimulated hypertrophic neonatal rat cardiomyocytes (NRCMs). The TAC-induced hypertrophy and LV dysfunction were aggravated in global and cardiac specific knockout of UCP3 (UCP3cKO) mice but improved by cardiac specific overexpression of UCP3 (UCP3cOE). Similar alterations in hypertrophy were observed in PE-treated NRCMs with UCP3-knockdown/overexpression. Moreover, the TAC-increased aspartate and glutamic-oxaloacetic transaminase 2 (GOT2) activity were enhanced in UCP3cKO hearts but reversed in UCP3cOE ones. PE-induced increases of GOT2 activity were enhanced in the UCP3-knockdown NRCMs but attenuated in the UCP3 overexpression ones, accompanied with the downregulation of aspartate. The endogenous interaction of UCP3 and GOT2 was weakened in the PE-treated NRCMs compared with the PE-untreated cells. Furthermore, aspartate supplementation reversed the UCP3 overexpression-attenuated hypertrophy in the PE-stimulated NRCMs. In conclusion, UCP3 expression is downregulated in hypertrophic hearts and cardiomyocytes, whereas the increase of UCP3 mitigates cardiac hypertrophy by downregulation of the enhanced aspartate. These findings provide new knowledge for the function of UCP3 and therapeutic target for cardiac hypertrophy.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"202 ","pages":"Pages 1-12"},"PeriodicalIF":4.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143557164","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":"Corrigendum to “Activation of IGF-1 receptors and Akt signaling by systemic hyperinsulinemia contributes to cardiac hypertrophy but does not regulate cardiac autophagy in obese diabetic mice” [Journal of Molecular and Cellular Cardiology 113 (2017) 39–50].","authors":"Karla Maria Pires ,&nbsp;Marcio Buffolo ,&nbsp;Christin Schaaf ,&nbsp;J. David Symons ,&nbsp;James Cox ,&nbsp;E. Dale Abel ,&nbsp;Craizzg H. Selzman ,&nbsp;Sihem Boudina","doi":"10.1016/j.yjmcc.2025.01.008","DOIUrl":"10.1016/j.yjmcc.2025.01.008","url":null,"abstract":"","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"201 ","pages":"Page 94"},"PeriodicalIF":4.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin stimulation by collagen I at the progenitor stage accelerates maturation of human iPSC-derived cardiomyocytes","authors":"Carlos Barreto-Gamarra,&nbsp;Maribella Domenech","doi":"10.1016/j.yjmcc.2025.02.009","DOIUrl":"10.1016/j.yjmcc.2025.02.009","url":null,"abstract":"<div><div>Cell manufacturing challenges have hampered effective preclinical evaluations of mature cardiac cells derived from human-induced pluripotent stem cells (hiPSCs). These challenges mainly stem from standard differentiation methods yielding cardiac cells of an immature phenotype, low cell yields and the need for extended culture for enhanced maturation. Although the intricate relationship between extracellular matrix (ECM) components and integrin expression levels plays a pivotal role during heart development, the impact of differentiation and maturation of cardiac cells on integrin behavior has not been thoroughly studied. This study postulates that cardiac cell maturation is significantly influenced by the timing of integrin stimulation via cell-matrix interactions. We profiled integrin expression levels throughout the differentiation process of cardiac cells and assessed the effects of utilizing defined ECM components as culture substrates on cell adhesion, proliferation, differentiation, and maturation. Our findings reveal that integrins facilitate hiPSC adhesion to ECM coated culture surfaces and underscores dynamic alterations in integrin expression during cardiac cell differentiation. Remarkably, we observed significant enrichments in α2 and β1 collagen integrin levels at the progenitor and differentiated stages. These shifts in collagen integrin levels were associated with enhanced cell seeding efficiency on collagen-type I surfaces and altered population doubling times. The stimulation of collagen integrins at the progenitor stage markedly boosted cardiac cell maturation, demonstrated by a significant (∼3-fold) increase in cardiac troponin I expression compared to the standard method after 15 days of culture. Enhanced maturation levels were further supported by significant increases in sarcomere development, maturation gene expression, morphological features, improved beating potency, and fatty acid metabolism dependency. Cardiac maturation driven by collagen was abrogated upon inhibition of collagen integrins targeted with selective pharmacological blockers, affirming their indispensable role in maturation without affecting cardiac differentiation levels. Our work confirms that stimulating collagen integrins at the progenitor stage is a potential strategy to achieve rapid maturation of hiPSC-derived cardiac cells.</div></div><div><h3>Statement of significance</h3><div>This study offers a novel strategy guided by integrin expression levels for generating hiPSC-CMs with improved maturation features in a short culture period (&lt;16 days). The improvements in cardiac cell maturation were achieved by stimulating collagen type 1 integrin at the progenitor stage. The potential benefits of this method for regenerative cardiac repair will pave the way for the preclinical examination of mature cardiac cells in tissues to advance cell manufacturing and cardiac toxicity studies.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"201 ","pages":"Pages 70-86"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipotoxicity as a therapeutic target in the type 2 diabetic heart","authors":"Trang Van T. Luong,&nbsp;Seonbu Yang,&nbsp;Jaetaek Kim","doi":"10.1016/j.yjmcc.2025.02.010","DOIUrl":"10.1016/j.yjmcc.2025.02.010","url":null,"abstract":"<div><div>Cardiac lipotoxicity, characterized by excessive lipid accumulation in the cardiac tissue, is a critical contributor to the pathogenesis of diabetic heart. Recent research has highlighted the key mechanisms underlying lipotoxicity, including mitochondrial dysfunction, endoplasmic reticulum stress, inflammation, and cell apoptosis, which ultimately impair the cardiac function. Various therapeutic interventions have been developed to target these pathways, mitigate lipotoxicity, and improve cardiovascular outcomes in diabetic patients. Given the global escalation in the prevalence of diabetes and the urgent demand for effective therapeutic approaches, this review focuses on how targeting cardiac lipotoxicity may be a promising avenue for treating diabetes.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"201 ","pages":"Pages 105-121"},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531401","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":"Gain and loss of the centrosomal protein taxilin-beta influences cardiac proteostasis and stress","authors":"Jared M. McLendon ,&nbsp;Xiaoming Zhang ,&nbsp;Colleen S. Stein ,&nbsp;Leslie M. Baehr ,&nbsp;Sue C. Bodine ,&nbsp;Ryan L. Boudreau","doi":"10.1016/j.yjmcc.2025.02.008","DOIUrl":"10.1016/j.yjmcc.2025.02.008","url":null,"abstract":"<div><div>Centrosomes localize to perinuclear foci where they serve multifunctional roles, arranging the microtubule organizing center (MTOC) and anchoring ubiquitin proteasome system (UPS) machinery, as suggested by prior studies. In mature cardiomyocytes, centrosomal proteins redistribute into a specialized perinuclear cage-like structure, and a potential centrosomal-UPS interface has not been studied, despite established roles for UPS in cardiomyopathy. In addition, there have been no reports citing cardiomyocyte UPS dysfunction upon or after manipulation of centrosomal proteins. Taxilin-beta (Txlnb), a cardiomyocyte-enriched protein, belongs to a family of centrosome adapter proteins implicated in protein quality control. We hypothesize that Txlnb is part of the perinuclear centrosomal cage and regulates proteostasis in cardiomyocytes. Herein, we show that centrosome proteins, including Txlnb, have significantly broadly dysregulated RNA expressions in failing hearts; however, Txlnb protein levels appear to be unchanged. Reanalysis of Txlnb's interactome supports its involvement in cytoskeletal, microtubule, and UPS processes, particularly centrosome-related functions. Using gain and loss of function approaches, in cells and mice, we show that Txlnb is a novel regulator of cardiac proteostasis through its influence on UPS. Overexpressing Txlnb in cardiomyocytes reduces ubiquitinated protein accumulation and enhances proteasome activity during hypertrophy. Germline Txlnb knockout in mice increases ubiquitinated protein accumulation, decreases 26Sβ5 proteasome activity, and lowers cardiac mass with aging, indicating proteasomal insufficiency and altered cardiac growth. Loss of Txlnb worsens heart phenotypes in mouse models of cardiac proteotoxicity and pressure overload. Overall, our data implicate the centrosomal protein Txlnb as a novel regulator of cardiac proteostasis, highlighting the likely presence of an understudied and important centrosome-proteasome functional connection in cardiomyocytes.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"201 ","pages":"Pages 56-69"},"PeriodicalIF":4.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511237","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":"Experimental pressure overload induces a cardiac neoantigen specific humoral immune response","authors":"Sasha Smolgovsky ,&nbsp;Abraham L. Bayer ,&nbsp;Mark Aronovitz ,&nbsp;Kathleen M.M. Vanni ,&nbsp;Annet Kirabo ,&nbsp;David G. Harrison ,&nbsp;Pilar Alcaide","doi":"10.1016/j.yjmcc.2025.02.007","DOIUrl":"10.1016/j.yjmcc.2025.02.007","url":null,"abstract":"<div><div>Inflammation is a hallmark of heart failure (HF), however anti-inflammatory therapies have yet to translate clinically. T-cells are central to cardiac pathology in experimental models of HF with reduced and preserved ejection fraction (HFrEF and HFpEF), however their antigen requirements differ, as shown in previous studies. Here we demonstrate that pressure overload elicits a cardiac and lymphoid B-cell humoral response characterized by autoantibodies (AAbs) towards the same cardiac neoantigens that induce T-cells in an experimental model of HFrEF, a novel mechanism distinct from an experimental model of HFpEF.</div></div>","PeriodicalId":16402,"journal":{"name":"Journal of molecular and cellular cardiology","volume":"201 ","pages":"Pages 87-93"},"PeriodicalIF":4.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143501939","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}