Cardiovascular Research最新文献

{"title":"Bone morphogenetic protein 10 is increased in precapillary pulmonary hypertension patients.","authors":"Aida Llucià-Valldeperas, Jessie van Wezenbeek, Joanne A Groeneveldt, Rowan Smal, Gonzalo Sánchez-Duffhues, Clarissa Becher, Azar Kianzad, Samara M A Jansen, Jeroen N Wessels, M Louis Handoko, Lilian J Meijboom, J Tim Marcus, Petr Symersky, Hans W M Niessen, Anton Vonk-Noordegraaf, Harm Jan Bogaard, Marie José Goumans, Frances S de Man","doi":"10.1093/cvr/cvaf028","DOIUrl":"https://doi.org/10.1093/cvr/cvaf028","url":null,"abstract":"<p><strong>Aims: </strong>Precapillary pulmonary hypertension (precPH) results in increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults, primarily produced by RA cardiomyocytes. The aim of this study was to investigate BMP10 expression in the right heart and systemic circulation and to identify potential triggers for increased BMP10 secretion associated with precPH.</p><p><strong>Methods and results: </strong>We examined BMP10 mRNA and protein expressions in RA tissue. Circulating BMP10 plasma levels were determined using ELISA. BMP10 transcriptional activity was studied using a BRE-Luciferase assay. Correlation analyses were performed between circulating BMP10 and RA dilatation as well as right ventricular (RV) function. Finally, we determined the impact of pressure unloading on BMP10 activity in Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients before and after pulmonary endarterectomy (PEA).BMP10 mRNA, protein and activity were significantly increased in the precPH right atrium. While circulating BMP10 protein levels were elevated, no significant changes were observed in BMP10 transcriptional activity between precPH and controls. Interestingly, RA dilatation, increased RA pressure, high NTproBNP levels and reduced RV ejection fraction were associated with high BMP10 activity. Finally, pressure unloading after PEA in a cohort of CTEPH patients, resulted in reduced BMP10 activity.</p><p><strong>Conclusions: </strong>In conclusion, RA BMP10 expression and plasma levels are increased in precPH, likely triggered by excessive RA dilatation and pressure overload. Future studies are needed to determine whether increased BMP10 release is an adaptive mechanism or a potential therapeutic target.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482388","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 Mediterranean diet displays an immunomodulatory effect that correlates with beneficial changes in carotid atherosclerosis.","authors":"Ana María Ruiz-León, Miguel Camafort, Aleix Sala-Vila, Rosa Gilabert, Isabel Núñez, Sara Castro-Barquero, Montserrat Fitó, Rosa María Lamuela-Raventós, Xavier Pintó, Ana García-Arellano, Emilio Ros, Ramon Estruch, Rosa Casas","doi":"10.1093/cvr/cvaf027","DOIUrl":"https://doi.org/10.1093/cvr/cvaf027","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482389","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":"Restoring balance with recombinant interleukin-37: hope for halting chronic inflammation in calcific aortic valve disease.","authors":"Nalin H Dayawansa, Sara Baratchi, Karlheinz Peter","doi":"10.1093/cvr/cvaf018","DOIUrl":"https://doi.org/10.1093/cvr/cvaf018","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490901","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":"Endothelial c-REL orchestrates atherosclerosis at regions of disturbed flow through crosstalk with TXNIP-p38 and non-canonical NF-κB pathways.","authors":"Blanca Tardajos Ayllon, Neil Bowden, Celine Souilhol, Hazem Darwish, Siyu Tian, Carrie Duckworth, D Mark Pritchard, Suowen Xu, Jon Sayers, Sheila Francis, Jovana Serbanovic-Canic, Fiona Oakley, Paul C Evans","doi":"10.1093/cvr/cvaf024","DOIUrl":"https://doi.org/10.1093/cvr/cvaf024","url":null,"abstract":"<p><strong>Aims: </strong>Atherosclerosis initiation at sites of disturbed blood flow involves heightened inflammation coupled to excessive endothelial cell (EC) proliferation. Here, we unveil the pivotal role of c-REL, a member of the NF-κB transcription factor family, in orchestrating these processes by driving dual pathological inflammatory and cell cycle pathways.</p><p><strong>Methods and results: </strong>Analysis of cultured EC and murine models revealed enrichment and activation of c-REL at atherosusceptible sites experiencing disturbed flow. Transcriptome analysis, extensively validated in vitro and in vivo, demonstrates that endothelial c-REL drives inflammation via a TXNIP-p38 MAP kinase signalling pathway and enhances proliferation through a non-canonical NFKB2-p21 pathway. Consistent with its pivotal role in EC pathology, genetic deletion of c-Rel in EC significantly reduces plaque burden in hypercholesterolemic mice.</p><p><strong>Conclusions: </strong>These findings underscore the fundamental role of c-REL in endothelial responses to disturbed flow and highlight therapeutic targeting of endothelial c-REL as a potential strategy for atherosclerosis treatment.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467174","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":"METTL3-catalyzed m6A methylation facilitates the contribution of vascular smooth muscle cells to atherosclerosis","authors":"Zhigang Dong, Yourong Jin, Yicong Shen, Jiaqi Huang, Jiaai Tan, Qianqian Feng, Ze Gong, Shirong Zhu, Huiyue Chen, Fang Yu, Wei Li, Yiting Jia, Wei Kong, Yi Fu","doi":"10.1093/cvr/cvaf029","DOIUrl":"https://doi.org/10.1093/cvr/cvaf029","url":null,"abstract":"Aims Vascular smooth muscle cells (VSMCs) are involved in the etiology of atherosclerosis, but whether methyltransferase-like 3 (METTL3)-catalyzed N6-methyladenosine (m6A) modulates the contribution of VSMCs to atherosclerosis remains elusive. Methods and Results We generated tamoxifen-inducible VSMC-specific METTL3 knockout mice with VSMC lineage tracing, and found that VSMC-specific METTL3 deficiency substantially attenuated atherosclerosis and reduced the proportion of VSMCs in plaques, due to the inhibition of VSMC atheroprone phenotype as characterized by macrophage-like and inflammatory features as well as high migratory and proliferative capacity. m6A-methylated RNA immunoprecipitation sequencing (MeRIP-Seq) combined with polysome profiling analysis mechanistically displayed METTL3 catalyzed m6A methylation of myocardin-related transcription factor A (MRTFA) mRNA, and further enhanced YTH N6-methyladenosine RNA binding protein F3 (YTHDF3)-dependent MRTFA mRNA translation. Conversely, adenovirus or adeno-associated virus-mediated VSMC-specific MRTFA overexpression abolished METTL3 deficiency-mediated alleviation of VSMC atheroprone phenotypic switching and atherosclerotic progression both in vitro and in vivo. Conclusion METTL3 facilitated the contribution of VSMCs to atherosclerosis through the m6A-YTHDF3-dependent MRTFA mRNA translation enhancement.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"52 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462805","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":"TAOK1 suppression improves doxorubicin-induced cardiomyopathy by preventing cardiomyocyte death and dysfunction","authors":"Takaomi Suga, Tomoya Kitani, Masaya Kogure, Masatsugu Oishi, Fumiaki Ito, Atsushi Hoshino, Takehiro Ogata, Koji Ikeda, Satoaki Matoba","doi":"10.1093/cvr/cvaf022","DOIUrl":"https://doi.org/10.1093/cvr/cvaf022","url":null,"abstract":"Aims Doxorubicin (DOX) is one of the most effective chemotherapeutic agents for various types of cancers. However, DOX often causes cardiotoxicity, which is referred to as DOX-induced cardiomyopathy (DIC). Despite extensive research, only a limited number of effective treatments are currently available. In this study, we aimed to identify a potential therapeutic target for DIC by preventing DOX-induced cell injury in cardiomyocytes. Methods and results We performed a kinome-wide CRISPR gene knockout screen in human cardiomyocytes derived from pluripotent stem cells (hPSC-CMs) and identified a member of the STE20 kinase family, thousand and one amino acid protein kinase 1 (TAOK1) as a potential regulator of DOX-induced cardiomyocyte death. Using CRISPR-mediated gene knockout and siRNA-mediated gene knockdown, we demonstrated that TAOK1 suppression improved DOX-induced cardiomyocyte death and dysfunction, including sarcomere disarray, contractile dysfunction, DNA damage, and mitochondrial dysfunction in hPSC-CMs. Transcriptome analysis using RNA-Seq also showed that DOX-induced mitochondrial dysfunction was attenuated by TAOK1 suppression. In contrast to the protective role of TAOK1 against DOX toxicity in cardiomyocytes, TAOK1 suppression did not induce DOX resistance in human cancer cell lines. DOX-induced activation of p38 MAPK was markedly attenuated in TAOK1-knockout hPSC-CMs. Furthermore, DOX-induced cardiomyocyte death and disruption of mitochondrial membrane potential were augmented by TAOK1 overexpression, which was partially attenuated by an inhibitor or knockdown of p38 MAPK or an apoptosis inhibitor. Finally, we demonstrated that TAOK1 suppression using AAV-mediated gene silencing attenuated DOX-induced myocardial damage, including myocardial fibrosis, apoptosis, and cardiomyocyte atrophy, resulting in improved cardiac function in a mouse model of DIC. Conclusion Our results indicate that TAOK1 suppression is a promising therapeutic approach for treating DIC in patients with cancer and highlight the advantages of hPSC-CMs as a platform to study drug-induced cardiotoxicity.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"29 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443241","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":"Cardiomyocyte SORBS2 expression increases in heart failure and regulates integrin interactions and extracellular matrix composition.","authors":"Louk T Timmer, Elvira den Hertog, Danielle Versteeg, Harm Post, Job A J Verdonschot, Jantine Monshouwer-Kloots, Eirini Kyriakopoulou, Ilaria Perini, Tim Koopmans, Petra van der Kraak, Lorena Zentilin, Stephane R B Heymans, Aryan Vink, Mauro Giacca, Albert J R Heck, Eva van Rooij","doi":"10.1093/cvr/cvaf021","DOIUrl":"10.1093/cvr/cvaf021","url":null,"abstract":"<p><strong>Aims: </strong>In this study, we aimed to uncover genes associated with stressed cardiomyocytes by combining single-cell transcriptomic datasets from failing cardiac tissue from both humans and mice.</p><p><strong>Methods and results: </strong>Our bioinformatic analysis identified SORBS2 as conserved NPPA correlated gene. Using mouse models and cardiac tissue from human heart failure patients, we demonstrated that SORBS2 expression is consistently increased during pathological remodeling, correlates to disease severity and is regulated by GATA4. By affinity-purification mass-spectrometry, we showed SORBS2 to interact with the integrin-cytoskeleton connections. Cardiomyocyte-specific genetic loss of Sorbs2 in adult mice changed integrin interactions, indicated by the increased expression of several integrins and altered extracellular matrix components connecting to these integrins, leading to an exacerbated fibrotic response during pathological remodeling.</p><p><strong>Conclusions: </strong>Sorbs2 is a cardiomyocyte-enriched gene that is increased during progression to heart failure in a GATA4-dependent manner and correlates to phenotypical hallmarks of cardiac failure.Our data indicate SORBS2 to function as a crucial regulator of integrin interactions and cardiac fibrosis.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432546","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":"Angiotensin 1-7 and a TERT activator individually restore vasodilatory capacity within the microcirculation previous SARS-CoV-2 infection.","authors":"Yoshinori Nishijima, Shelby N Hader, Erin C Birch, Yiliang Chen, Michael E Widlansky, Andreas M Beyer","doi":"10.1093/cvr/cvaf020","DOIUrl":"https://doi.org/10.1093/cvr/cvaf020","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405702","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":"Stretch regulation of β2-Adrenoceptor signalling in cardiomyocytes requires caveolae.","authors":"Jiarong Fu, Catherine Mansfield, Ivan Diakonov, Aleksandra Judina, Matthew Delahaye, Navneet Bhogal, Jose L Sanchez-Alonso, Timothy Kamp, Julia Gorelik","doi":"10.1093/cvr/cvae265","DOIUrl":"https://doi.org/10.1093/cvr/cvae265","url":null,"abstract":"<p><strong>Aims: </strong>Caveolin-3 is essential for the formation of caveolae in cardiomyocytes. Caveolar microdomains have been shown to regulate the distribution of signalling proteins such as beta-adrenoceptors (βAR) and may act as membrane reserves to protect the cell from damage during the mechanical stretch. Myocardial stretch occurs during haemodynamic overload and may be normal (e.g. exercise) or pathological (e.g. heart failure); therefore, it is important to understand the effect of stretch on signalling pathways associated with mechanosensitive structures, such as caveolae. In this study, we investigate the role of caveolae in regulating the effect of stretch on βAR-signalling.</p><p><strong>Methods and results: </strong>We used osmotic swelling of isolated rat ventricular cardiomyocytes as a method to stretch the cell membrane and investigate the effect of βAR stimulation on cyclic adenosine monophosphate (cAMP) activity and contractility. βAR response was measured using a Förster Resonance Energy Transfer reporter for the second messenger cAMP and using CytoCypher for the measurement of cell contractility. β1AR and β2AR blockers were used to selectively allow stimulation of β2AR and β1AR, respectively. We also investigated the effect of stretch on βAR response to isoprenaline stimulation in left ventricular trabeculae dissected from control and cardiac-specific caveolin-3 knock-out mice (Cav3KO). Stretching trabeculae produces increased baseline adenylyl cyclase activity and a higher level of cAMP and a greater β2AR-induced positive inotropy after stimulation of the β2AR but not β1AR, by isoprenaline. Similar findings were confirmed for isolated myocytes subjected to hypoosmotic conditions. In isolated cardiomyocytes, caveolae depletion using methyl-beta-cyclodextrin or Cav3KO abolished the increase in β2AR response induced by stretch.</p><p><strong>Conclusion: </strong>Our study reveals a stretch-regulation of the β2AR signalling pathway, which requires functional caveolae. This indicates caveolae are mechanosensitive membrane domains that undergo structural and functional changes in response to stretch, thus leading to mechanical regulation of caveolae-associated signalling pathways.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405715","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":"Colchicine and stabilization of coronary artery plaques.","authors":"Valtteri Muroke, Jean-Claude Tardif","doi":"10.1093/cvr/cvaf019","DOIUrl":"https://doi.org/10.1093/cvr/cvaf019","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405705","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}