Circulation research最新文献

{"title":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000731","DOIUrl":"https://doi.org/10.1161/RES.0000000000000731","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 7","pages":"931-933"},"PeriodicalIF":16.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039261","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":"Targeting Kinin B1R Attenuates Hypertension Through AT1R-Dependent Mechanisms.","authors":"Drew Theobald, Riley N Bessetti, Yumei Feng Earley, Eric Lazartigues, Karen Litwa, Srinivas Sriramula","doi":"10.1161/CIRCRESAHA.125.326648","DOIUrl":"10.1161/CIRCRESAHA.125.326648","url":null,"abstract":"<p><strong>Background: </strong>Neurogenic hypertension is chronically high blood pressure that is initiated and maintained through excessive sympathetic nervous system activity and has been associated with increased B1R (kinin B1 receptor) activation. We previously reported a central role for B1R in mediating inflammatory pathways in the development of deoxycorticosterone acetate salt hypertension. Additionally, we identified a causal relationship between B1R expression after Ang II (angiotensin II) stimulation, and that B1R can mediate the bidirectional interaction between neuroinflammation and oxidative stress. However, whether there are any interactions between AT1R (Ang II-type I receptor) and B1R, and if B1R can mediate the effects of Ang II-induced hypertension, has not yet been investigated.</p><p><strong>Methods: </strong>We used a well-established mouse model of Ang II-induced hypertension to test the hypothesis that B1R activation contributes to increased sympathoexcitation, autonomic dysfunction, oxidative stress, and inflammation, potentially through interactions with AT1R. Wild-type and BIR knockout mice were infused with Ang II or saline via osmotic minipump for 28 days, then functional and molecular changes in response to Ang II were assessed.</p><p><strong>Results: </strong>Ang II in wild-type mice led to significant increases in B1R expression associated with sympathoexcitation, autonomic dysfunction, impaired baroreflex sensitivity, and enhanced blood pressure, whereas these changes were attenuated in B1R gene-deficient mice. B1R was shown to directly interact with AT1R, and activation of B1R was involved with microglial activation and subsequent neuroinflammation, increased neuronal firing, and altered synaptic density. We further used pharmacological blockade of B1R to dismiss potential developmental alterations in gene-deficient mice. Specific B1R antagonist attenuated Ang II-induced increases in blood pressure, supporting the role of B1R in blood pressure regulation.</p><p><strong>Conclusions: </strong>Our data provide the first evidence of the role of B1R in Ang II-induced hypertension and its interactions with AT1R, highlighting B1R as a potential therapeutic target for hypertension.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"950-966"},"PeriodicalIF":16.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882220","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":"Correction to: Klotho Deficiency Causes Heart Aging via Impairing the Nrf2-GR Pathway.","authors":"Kai Chen, Shirley Wang, Qiwei Wilton Sun, Bo Zhang, Mujib Ullah, Zhongjie Sun","doi":"10.1161/RES.0000000000000730","DOIUrl":"https://doi.org/10.1161/RES.0000000000000730","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 7","pages":"e175"},"PeriodicalIF":16.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039276","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":"Melanocortin System Activates Carotid Body Arterial Chemoreceptors in Hypertension.","authors":"Audrys G Pauza, Pratik Thakkar, Xin Shen, Igor S A Felippe, Kilian Roßmann, Manami Oya, Fiona D McBryde, Kazuhiro Nakamura, Johannes Broichhagen, David J Hodson, Dainius H Pauza, David Murphy, Julian F R Paton","doi":"10.1161/CIRCRESAHA.125.326394","DOIUrl":"10.1161/CIRCRESAHA.125.326394","url":null,"abstract":"<p><strong>Background: </strong>The internal milieu of the body is controlled by a system of interoceptors coupled to motor outflows that drive compensatory adaptive responses. These include the arterial chemoreceptors, best known for sensing arterial oxygen. In cardiometabolic diseases, such as essential hypertension, the carotid bodies (CB) exhibit heightened reflex sensitivity and tonic activity without an apparent stimulus. The mechanisms behind CB sensitization in these conditions are not well understood.</p><p><strong>Methods: </strong>Guided by functional genomics, a range of functional assays is used to interrogate downstream intracellular and interorgan signaling pathways involved in arterial chemosensory function.</p><p><strong>Results: </strong>Here, we report the presence of the MC4R (melanocortin 4 receptor) in the mammalian CB and show its elevated expression in experimental hypertension. We demonstrate that melanocortin agonists activate arterial chemosensory cells, modulating CB chemosensory afferent drive to influence chemoreflex-evoked sympathetic and ventilatory activity. Transcriptional analysis of hypertensive CB implicates the activation of the Mash1 (mammalian achaete-scute homolog 1; <i>Ascl1</i>) regulatory network in driving elevated <i>Mc4r</i> expression.</p><p><strong>Conclusions: </strong>Collectively, our data indicate a primarily pathophysiological role of melanocortin signaling in arterial chemosensation, contributing to excess sympathetic activity in cardiometabolic disease.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"967-982"},"PeriodicalIF":16.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944789","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":"RBPMS and RBPMS2 Cooperate to Safeguard Cardiac Splicing.","authors":"Tongbin Wu, Zeyu Chen, Chao Gao, Elise V Stanley, Zengming Zhang, Yusu Gu, Xiaohai Zhou, Ju Chen","doi":"10.1161/CIRCRESAHA.125.326948","DOIUrl":"10.1161/CIRCRESAHA.125.326948","url":null,"abstract":"<p><strong>Background: </strong>Mutations in cardiac SFs (splicing factors) cause cardiomyopathy and congenital heart disease, underscoring the critical role of SFs in cardiac development and disease. Cardiac SFs are implicated to cooperatively regulate the splicing of essential cardiac genes, but the functional importance of their collaboration remains unclear. RBPMS (RNA-binding protein with multiple splicing) and RBPMS2 (RNA-binding protein with multiple splicing 2) are SFs involved in heart development and exhibit similar splicing regulatory activities in vitro, but it is unknown whether they cooperate to regulate splicing in vivo.</p><p><strong>Methods: </strong><i>Rbpms</i> and <i>Rbpms2</i> single- or double-cardiomyocyte-specific knockout (KO) mice were generated and analyzed for cardiac phenotypes. RNA sequencing was performed to assess gene expression and splicing changes in single and double KOs. In silico analyses and minigene splicing assays were used to dissect the mechanisms underlying the roles of RBPMS and RBPMS2 in heart development.</p><p><strong>Results: </strong>Mice lacking both RBPMS and RBPMS2 in cardiomyocytes died before embryonic day 13.5 and developed sarcomere disarray, whereas <i>Rbpms</i> or <i>Rbpms2</i> single-cardiomyocyte-specific KO mice had normal sarcomere assembly and survived to adulthood. Defective sarcomere assembly is likely owing to the widespread mis-splicing of genes essential for cardiac contraction in double-KO mice, underscoring the overlapping role of RBPMS and RBPMS2 in splicing regulation. Mechanistically, we found that RBPMS and RBPMS2 collectively promote cardiac splicing programs while repressing noncardiac splicing programs. Moreover, RNA splicing maps suggested that the binding location of RBPMS and RBPMS2 on precursor messenger RNA dictates whether they function as splicing activators or repressors. Last, the sensitivity to the dosage of RBPMS and RBPMS2 for splicing regulation arises from intrinsic features of the target exons.</p><p><strong>Conclusions: </strong>Our results demonstrate that RBPMS and RBPMS2 work in concert to safeguard the splicing of genes essential for cardiac contraction, highlighting the importance of SF collaboration in maintaining cardiac splicing signature, which should be taken into consideration when devising future therapeutic approaches through modulating the activity of SFs.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"1027-1044"},"PeriodicalIF":16.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944787","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":"Beyond the Vessel Wall: Perivascular Adipose Tissue as a Guardian of Aorta.","authors":"Zhinan Wu,Wencheng Zhang","doi":"10.1161/circresaha.125.327184","DOIUrl":"https://doi.org/10.1161/circresaha.125.327184","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"24 1","pages":"1024-1026"},"PeriodicalIF":20.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035802","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":"Melanocortin Signaling in the Carotid Body as a Putative Cause of Hypertension.","authors":"Mateus R Amorim,Vsevolod Y Polotsky","doi":"10.1161/circresaha.125.327185","DOIUrl":"https://doi.org/10.1161/circresaha.125.327185","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"21 1","pages":"983-985"},"PeriodicalIF":20.1,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035804","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":"DWORF Gene Therapy Improves Cardiac Calcium Handling and Mitochondrial Function.","authors":"Omar Brito-Estrada,Yasuhide Kuwabara,Aaron M Gibson,Keira R Hassel,Michael L Kamradt,Joseph P Verry,N Scott Blair,Michael J Bround,Jiuzhou Huo,Jeffery D Molkentin,Catherine A Makarewich","doi":"10.1161/circresaha.125.326550","DOIUrl":"https://doi.org/10.1161/circresaha.125.326550","url":null,"abstract":"BACKGROUNDCalcium (Ca2+) dysregulation is a hallmark of heart failure, impairing excitation-contraction coupling and contributing to pathological remodeling. The SERCA2a (sarco/endoplasmic reticulum Ca2+ ATPase isoform 2a) mediates Ca2+ reuptake into the sarcoplasmic reticulum (SR) during diastole, but its activity declines in failing hearts. DWORF (dwarf open reading frame), a newly identified cardiac microprotein, enhances SERCA2a activity and improves cardiomyocyte Ca2+ cycling and contractility. SR Ca2+ release also influences mitochondrial metabolism and ATP production. Here, we investigated whether DWORF overexpression improves SR Ca2+ handling, augments mitochondrial Ca2+ signaling, and protects against heart failure progression.METHODSTransgenic and adeno-associated virus approaches were used to overexpress DWORF in the heart. Mice underwent transverse aortic constriction to model pressure overload-induced heart failure. Cardiac function, mitochondrial metabolism, SR Ca2+ uptake, and remodeling were assessed.RESULTSMitochondria from DWORF transgenic hearts displayed increased basal respiration, maximal respiration, and spare respiratory capacity, correlating with enhanced mitochondrial Ca2+ uptake kinetics. Western blot analysis showed elevated levels of active PDH (pyruvate dehydrogenase) and mitochondrial Ca2+ uniporter expression in DWORF transgenic hearts, supporting a role for DWORF in Ca2+-driven metabolic regulation. Similarly, MyoAAV-mediated DWORF overexpression enhanced mitochondrial respiration and increased levels of active PDH in adult mice. Following TAC, MyoAAV-DWORF-treated mice maintained higher left ventricular function and were protected from further deterioration compared with controls. This benefit was observed when DWORF gene therapy was delivered preventively at the time of pressure overload or after heart failure was already established. DWORF gene therapy also attenuated remodeling, with lower heart weight and lung weight-to-tibia length ratios. Seahorse analysis confirmed sustained mitochondrial improvements in both treatment paradigms.CONCLUSIONSDWORF overexpression enhances SR Ca2+ dynamics, improves mitochondrial energetics, and attenuates pathological remodeling and heart failure progression in response to pressure overload. These findings support DWORF as a promising therapeutic target for heart failure.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"14 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144995931","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":"Regulated Cell Death in Myocardial Infarction.","authors":"Richard N Kitsis","doi":"10.1161/CIRCRESAHA.125.323052","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.125.323052","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 6","pages":"924-929"},"PeriodicalIF":16.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944837","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":"Iron Lion ZIPion: ZIP13 Zips Iron to Heart Mitochondria.","authors":"Hualin Fan, Luca Scorrano","doi":"10.1161/CIRCRESAHA.125.327126","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.125.327126","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 6","pages":"863-865"},"PeriodicalIF":16.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944873","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}