Cardiovascular Research最新文献

{"title":"PLN-R14-del, a puzzling mutation.","authors":"A Zaza, C Maniezzi","doi":"10.1093/cvr/cvaf189","DOIUrl":"https://doi.org/10.1093/cvr/cvaf189","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257410","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":"AAV6-based ZEB2 delivery promotes cardiomyocyte dedifferentiation in adult human myocardium.","authors":"Rocco Caliandro,Azra Husetić,Merel L Ligtermoet,Jermo Hanemaaijer-van der Veer,Karel van Duijvenboden,Lorena Zentilin,Mara Clerkx,Mauro Giacca,Roelof-Jan Oostra,Maurice J B van den Hoff,Vincent M Christoffels,Monika M Gladka","doi":"10.1093/cvr/cvaf190","DOIUrl":"https://doi.org/10.1093/cvr/cvaf190","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"121 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261398","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":"Activated CaMKIIδ translocates to the RyR nanodomain in cardiomyocytes","authors":"Anna Bergan-Dahl, Cathrine R Carlson, Martin Laasmaa, Hariharan Subramanian, Adelle Basson, Jia Li, Almira Hasic, Marianne Lunde, Hege Ugland, Ornella Manfra, Enno Klussmann, Julie Bossuyt, Donald M Bers, Viacheslav O Nikolaev, William E Louch, Xin Shen","doi":"10.1093/cvr/cvaf187","DOIUrl":"https://doi.org/10.1093/cvr/cvaf187","url":null,"abstract":"Background The heartbeat is triggered by the coordinated release of Ca2+ from the ryanodine receptor type-2 (RyR) in cardiomyocytes. Phosphorylation of RyR by Ca2+/calmodulin-dependent kinase IIδ (CaMKIIδ) fine-tunes this process in health, while hyperphosphorylation causes excessive, pathological Ca2+ release. We investigated how CaMKIIδ is spatially recruited and anchored to RyRs to achieve this functional regulation. Methods We employed confocal and dSTORM microscopy to investigate the macro- and nanoscale distribution of CaMKIIδ across cardiomyocytes, respectively. We linked positional rearrangement of the kinase during β-adrenergic stimulation (isoproterenol, Iso) to alterations in RyR phosphorylation and function (Ca2+ sparks), and the requirement of the CaMKIIδ anchoring protein AKAP18δ by knockdown/knockout. Results Confocal microscopy revealed that macroscale CaMKIIδ localization was not markedly altered during Iso treatment, although a narrowing of its distribution around the Z-lines occurred, where the RyR reside. Higher resolution dSTORM imaging confirmed that local mobilization of CaMKIIδ by Iso decreased the distance from Z-lines and RyRs to the nearest CaMKIIδ by 28% and 12%, respectively. Functionally, kinase translocation into the RyR nanodomain was accompanied by increased channel phosphorylation and Ca2+ spark frequency. These actions were dependent on CaMKIIδ activity, since kinase translocation, RyR phosphorylation, and activation were all mimicked by the upstream activator of CaMKIIδ (8-CPT) and prevented by direct CaMKIIδ inhibitors (AIP, N1 peptide). A critical role of AKAP18δ in this mechanism was supported by immunoprecipitation experiments, which showed greater kinase binding to AKAP18δ during Iso stimulation. Furthermore, loss of AKAP18δ by viral-mediated AKAP18δ knockdown or knockout prevented CaMKIIδ translocation to Z-lines. Microtubular disruption also blocked CaMKIIδ translocation. Conclusions Collectively, our results indicate that nanoscale movement of CaMKIIδ is closely associated with RyR activation following β-adrenergic stimulation. This translocation depends on an intact microtubular network and kinase binding to AKAP18δ.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"18 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260613","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":"A RADical approach to treating heart failure.","authors":"Mohammed Obeidat,David A Eisner","doi":"10.1093/cvr/cvaf184","DOIUrl":"https://doi.org/10.1093/cvr/cvaf184","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"38 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261397","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":"The devil is in the details: addressing lung cell heterogeneity in Sugen-hypoxia rats and its relevance to pulmonary arterial hypertension.","authors":"Sucheta Chopra,Vinicio A de Jesus Perez","doi":"10.1093/cvr/cvaf188","DOIUrl":"https://doi.org/10.1093/cvr/cvaf188","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"115 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261452","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":"Cardiovascular risk factors and the allostatic interoceptive network in dementia","authors":"Jessica L Hazelton, Joaquín Migeot, Raul Gonzalez-Gomez, Florencia Altschuler, Claudia Duran-Aniotz, Olivia Wen, Dante Sebastián Galván Rial, Pablo Barttfeld, Vicente Medel, Cecilia González Campo, Ana María Castro-Laguardia, Hernán Hernández, Carolina Gonzalez-Silva, Olga Castaner, Kun Hu, Peng Li, María Isabel Behrens, Martin A Bruno, Juan Felipe Cardona, Nilton Custodio, Hernando Santamaria-Garcia, Adolfo M Garcia, Maria E Godoy, José Alberto Avila-Funes, Marce Maito, Diana L Matallana, Bruce Miller, Francisco Lopera, Maira Okada de Oliveira, Stefanie D Pina-Escudero, Katherine L Possin, Elisa de Paula France Resende, Pablo Reyes, Andrea Slachevsky, Ana Luisa Sosa, Leonel T Takada, Jennifer S Yokoyama, Agustín Ibanez","doi":"10.1093/cvr/cvaf185","DOIUrl":"https://doi.org/10.1093/cvr/cvaf185","url":null,"abstract":"Aims Cardiovascular risk factors, such diabetes, hypertension, blood pressure, obesity, and smoking, are linked with allostatic-interoception – the continuous monitoring of internal bodily states in anticipation of environmental demands. These risk factors are associated with dementia risk. How these factors affect brain networks vulnerable to neurodegeneration and involved in allostatic-interoception, such as the Allostatic-Interoceptive Network (AIN), is unknown. We investigated the relationship between cardiovascular risk and AIN structure and function in frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Methods and Results We recruited 1501 participants (304 with FTLD, 512 with AD, and 685 healthy controls) from the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). A cardiovascular risk score was calculated based on: age, sex, diabetes, hypertension, systolic blood pressure, body mass index, and smoking status. Cardiovascular risk was associated with gray matter integrity and functional connectivity in age- and sex-matched patient-control groups focusing on predefined regions of interest within the AIN. Higher cardiovascular risk was associated with reduced structural integrity and functional connectivity within the AIN in both FTLD and AD. FTLD patients showed more extensive structural and functional connectivity disruptions throughout the AIN. In AD patients, structural reductions in the AIN were prominent, with functional connectivity restricted to the hippocampus, parahippocampal gyrus, and orbitofrontal regions Conclusions Cardiovascular risk factors appear to adversely impact the AIN structure and function, with disease-specific patterns of vulnerability. Results underscore the importance of integrating cardiovascular health into models of neurodegenerative disease and managing cardiovascular health to support brain integrity in dementia.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"87 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260611","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":"Defining the safety belt for stroke thrombolysis: Preclinical validation of citPA5 across species and hemorrhagic scenarios.","authors":"Longguang Jiang,Cai Yuan,Mingdong Huang","doi":"10.1093/cvr/cvaf183","DOIUrl":"https://doi.org/10.1093/cvr/cvaf183","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"142 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240959","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":"Global, regional, and national burden of aortic aneurysm in the elderly from 1990 to 2021, and projections to 2050: a systematic analysis based on the 2021 Global Burden of Disease Study.","authors":"Cong Hu,Shuxiong Nong,Qi Zhang,Xiuhua Zhang,Chongkai Lin,Cai Huang,Chilin Liao,Meng Wu","doi":"10.1093/cvr/cvaf182","DOIUrl":"https://doi.org/10.1093/cvr/cvaf182","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"3 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226658","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":"CTLA-4-Ig therapy preserves cardiac function following myocardial infarction with reperfusion.","authors":"Jonathan Noonan, Shania A Prijaya, Laura A Bienvenu, Nalin H Dayawansa, Marcel Michla, Viktoria Bongcaron, Prerna Sharma, Yuyang Song, Angela Huang, Anastasia Barbaro-Wahl, Yilu Huang, Hung Nguyen, Anne Nguyen, Andrew J Murphy, Yiyu Zhang, Man K S Lee, Chad J Johnson, Anna M D Watson, Anita C Thomas, James D McFadyen, Daniel G Donner, Xiaowei Wang, Karlheinz Peter","doi":"10.1093/cvr/cvaf165","DOIUrl":"https://doi.org/10.1093/cvr/cvaf165","url":null,"abstract":"<p><strong>Aims: </strong>T cells drive adverse cardiac inflammation and ischemia-reperfusion injury following myocardial infarction (MI). Here, we aimed to test the extent to which T cell inhibition protected cardiac function following MI in mice.</p><p><strong>Methods and results: </strong>Cardiac ischemia-reperfusion injury (CIRI), mimicking MI with successful reperfusion therapy, was induced in C57BL/6J mice via temporary surgical ligation of the left anterior descending artery. T cell inhibition was achieved using abatacept, an FDA-approved CTLA-4-Ig fusion protein. Multiple treatment strategies were assessed, ranging from prolonged treatment across 4 weeks to short-term treatment, also with delayed time-to-intervention. Cardiac function was assessed using echocardiography, including strain analysis. Impacts on the cardiac and systemic immune response were assessed using flow cytometry. CIRI-induced robust CD4+ biased T cell activation in the heart within 7 days. Treatment with abatacept significantly preserved key echocardiographic metrics of cardiac function. This treatment coincided with near-complete inhibition of the cardiac T cell response, as well as reductions in innate inflammatory cells. Collectively, this demonstrated a central mechanistic role for T cell activation post-MI with reperfusion. Evaluation of short-term intervention strategies further demonstrated sustained preservation of cardiac function even where treatment was delayed by 24 h. Mechanistically, our data indicate that over 50% of lost cardiac function post-MI with reperfusion is T cell dependent.</p><p><strong>Conclusion: </strong>T cell co-stimulation leading to activation is a central driver of the cardiac immune response following MI with reperfusion. The inhibition of this axis significantly protected against CIRI and preserved cardiac function. Ultimately, we highlight T cell immunomodulation and abatacept as highly promising approaches for clinical translation.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211971","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":"Sympathovagal crosstalk: Y2-receptor blockade enhances vagal effects which in turn Reduce NPY levels via muscarinic receptor activation","authors":"Neil R Jani, Valerie Y H van Weperen, Thamali Ayagama, Jonathan D Hoang, Maryam Emamimeybodi, Benjamin Mothibe Bussmann, Sartaj Bal, Ashna Kumar, Artin Khaky, David Hamon, Neil Herring, Corey Smith, Marmar Vaseghi","doi":"10.1093/cvr/cvaf180","DOIUrl":"https://doi.org/10.1093/cvr/cvaf180","url":null,"abstract":"Aims Ventricular arrhythmias are associated with sympathoexcitation and increased co-transmitter neuropeptide Y (NPY) levels. Vagal nerve stimulation (VNS) has been reported to decrease release of norepinephrine, while NPY has been reported to decrease acetylcholine release ex-vivo by binding Y2 receptors on parasympathetic nerves. We hypothesized that VNS reduces NPY levels via a muscarinic receptor (MR) mediated mechanism in-vivo and that, in turn, blockade of presynaptic Y2R can further enhance the effects of VnS and decrease the effects of sympathoexcitation by increasing vagal tone. Methods &amp; Results Single-cell RNA sequencing of rat stellate ganglia and immunohistochemistry were performed and identified the M2 receptor as the predominant subtype on NPY-expressing sympathetic neurons. Ex-vivo field stimulation of rat stellate ganglia, before and after application of carbamylcholine (CCH; muscarinic agonist) and atropine (muscarinic blocker) showed that CCH reduced NPY release, while the addition of atropine increased NPY levels. Subsequently, to validate ex-vivo findings, in-vivo effects of VNS during bilateral stellate ganglia stimulation (BSS) on NPY release with and without atropine were evaluated and hemodynamic and electrophysiological parameters, including ventricular activation recovery intervals (ARIs, a surrogate for action potential duration), and real-time in-vivo interstitial NPY levels were measured. Post-atropine, suppression of NPY by VNS was significantly diminished, confirming a muscarinic receptor mediated mechanism in-vivo. Finally, in a porcine model in-vivo, effects of VNS on NPY levels and of the Y2R blocker, BIIE0246, during BSS were tested. These studies demonstrated that Y2R blockade significantly reduced the cardiac effects of BSS on systolic pressure, inotropy, and ARIs. While the ventricular effects of VNS, including suppression of interstitial NPY levels, hemodynamic, and electrophysiological parameters were enhanced by Y2R blockade, heart rate remained unaffected. Conclusion Vagal activation reduces interstitial NPY levels via a presynaptic sympathetic M2R mechanism.Y2R inhibition reduces effects of sympathoexcitation and enhances the effects of VNS in-vivo. These findings highlight the role of NPY in sympathovagal crosstalk and suggest Y2R as a potential target to modulate autonomic balance.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"19 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235369","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}