Cardiovascular Research最新文献

{"title":"Mimicked immunity: a strategy for targeted nanodrug delivery.","authors":"Yapei Zhang, Charles C Hong, Bryan Ronain Smith","doi":"10.1093/cvr/cvaf050","DOIUrl":"https://doi.org/10.1093/cvr/cvaf050","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794696","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":"Loss of conserved long non-coding RNA MIR503HG leads to altered NOTCH pathway signalling and left ventricular non-compaction cardiomyopathy","authors":"João P Monteiro, Diptarka Saha, Ana-Mishel Spiroski, Saiba Mahesh, Peter Kaltzis, Abhijit Nadavallil, Vaibhao Janbandhu, Nicholas J Murray, Francesco Severi, Azzurra Laura De Pace, Sandra Sánchez-Esteban, Julie Rodor, Abdelaziz Beqqali, Matthew Bennett, Kevin Stewart, Adrian Thomson, Patrick W F Hadoke, Dyana Markose, John R Wilson-Kanamori, Neil C Henderson, Dónal O’Carroll, Thomas Quertermous, Richard P Harvey, Gonzalo del Monte-Nieto, Andrew H Baker","doi":"10.1093/cvr/cvaf043","DOIUrl":"https://doi.org/10.1093/cvr/cvaf043","url":null,"abstract":"Aims The highly conserved long non-coding RNA (lncRNA) MIR505HG has been primarily recognized as a precursor for microRNAs (miR)-424 and miR-503. However, studies have since demonstrated that MIR503HG has distinct functions from its associated miRNAs, playing important roles in cell proliferation, invasion, apoptosis, and differentiation. While these miRNAs are known to influence cardiomyocyte differentiation, the specific role of MIR503HG in heart development remains unexplored. We seek to determine how MIR503HG deletion impacts ventricular chamber development and to identify underlying molecular mechanisms. Methods and results To study the role of the lncRNA in vivo, we generated a functional MIR503HG knockout mouse model (MIR503HG−/−) using a synthetic polyadenylation signal to terminate MIR503HG transcription without affecting miR-424/503 expression. We performed morphological analyses on embryonic and adult hearts using microCT along with cardiac functional analysis via transthoracic echocardiography. We further apply single-nuclei RNA sequencing (snRNA-seq) on adult hearts to identify potential molecular mechanisms underlying the observed phenotypes. Functional deletion of MIR503HG alone was associated with reduced compact myocardium thickness and increased trabecular myocardium in the left ventricle (LV) at embryonic day 17.5 compared to wild-type mice, indicating a LV non-compaction (LVNC) phenotype. Moreover, adult MIR503HG−/− mutant hearts showed increased trabecular complexity, impaired LV relaxation, and mitral valve regurgitation. SnRNA-seq further revealed altered expression of several genes associated with cardiomyocyte function and LVNC, including Actc1, Mib1, Mybpc3, and Myh7. Lastly, Notch1 activity was also significantly increased in mutant hearts which has been previously associated with LVNC. Conclusion MIR503HG plays a role in ventricular chamber development, and its deletion leads to an LVNC phenotype independent of the miRNA cluster within its locus, highlighting its importance in cardiac development and disease. We further suggest that abnormal Notch1 activity may underpin the LVNC phenotype presented.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"7 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775518","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":"Keep your guard up: blood-brain barrier protection by empagliflozin after acute ischaemic stroke.","authors":"Karin Hochrainer, Ashley Hansen, Lidia Garcia-Bonilla","doi":"10.1093/cvr/cvaf049","DOIUrl":"https://doi.org/10.1093/cvr/cvaf049","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771507","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":"Pre-ischaemic empagliflozin treatment attenuates blood-brain barrier disruption via β-catenin mediated protection of cerebral endothelial cells.","authors":"Guohao Liu, Yanmei Qiu, Nanlin You, Mengchen Yu, Wenbo Chen, Tao Sun, Zhen Qin, Mengtao Han, Zhiwei Xue, Xiangjun Liang, Bo Mao, Lu Ling, Yanzhao Wu, Wenchen Xing, Quanmeng Liu, Donghai Wang","doi":"10.1093/cvr/cvaf026","DOIUrl":"https://doi.org/10.1093/cvr/cvaf026","url":null,"abstract":"<p><strong>Aims: </strong>Microvascular endothelial cells dysfunction can significantly worsen ischaemic stroke outcomes by disrupting tight junctions and increasing the acquisition of adhesion molecules, accelerating blood-brain barrier (BBB) disruption and pro-inflammatory response. The identification of drugs that improve endothelial cell function may be crucial for ischaemic stroke. It has been validated that empagliflozin (EMPA), a novel antidiabetic drug, protects endothelial cells regardless of the diabetic status of the patient. However, the impact of EMPA on stroke outcomes is unclear. We hypothesized that EMPA would exert a beneficial effect on ischaemic stroke outcome by protecting microvascular endothelial cells against tight junction disruption and the increase of adhesion molecules.</p><p><strong>Methods and results: </strong>Young adult male mice were administered with EMPA or vehicle (dimethyl sulfoxide) daily for 7 days before being subjected to transient middle cerebral artery occlusion (tMCAO). Neurological deficits were evaluated for up to 28 days post-tMCAO. Infarct volume, BBB disruption, and inflammatory status were assessed 1 day after tMCAO.bEnd.3 cells and primary brain microvascular endothelial cells were treated with EMPA or vehicle under oxygen and glucose deprivation/reperfusion (OGD/R), and the lactate dehydrogenase release, transendothelial electrical resistance, leakage of fluorescein isothiocyanate-dextran, and tight junction and adhesion molecules proteins were examined. Mechanistic studies probing the effect of EMPA on endothelial cells were conducted by RNA-seq. EMPA treatment before ischaemia markedly improved infarct volume, BBB disruption, and inflammation 1-day post-tMCAO, and further enhanced neurobehavioral function up to 28 days. Pre-treatment of EMPA attenuated endothelial cell dysfunction under OGD/R conditions. In mechanistic terms, RNA-seq data from isolated cerebral microvessels revealed that the Wnt/β-catenin signalling pathway was preserved in the EMPA group, in contrast to the vehicle group. Pre-treatment with EMPA inhibited β-catenin ubiquitination and promoted β-catenin translocation from the cytoplasm to the nucleus to improve endothelial cell function. Importantly, the β-catenin inhibitor XAV-939 eliminated this protective function of EMPA.</p><p><strong>Conclusion: </strong>EMPA administration before tMCAO attenuated ischaemia/reperfusion-induced BBB disruption and inflammation via β-catenin-mediated protection of cerebral microvascular endothelial cells. Therefore, EMPA shows potential for improving stroke outcomes as an adjunctive preventive strategy.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771508","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 insulin-like growth factor-1 signaling regulates vascular barrier function and atherogenesis.","authors":"Michael Drozd, Alexander-Francisco Bruns, Nadira Y Yuldasheva, Azhar Maqbool, Hema Viswambharan, Anna Skromna, Natallia Makava, Chew W Cheng, Piruthivi Sukumar, Lauren Eades, Andrew M N Walker, Kathryn J Griffin, Stacey Galloway, Nicole T Watt, Natalie Haywood, Victoria Palin, Nele Warmke, Helen Imrie, Katherine Bridge, David J Beech, Stephen B Wheatcroft, Mark T Kearney, Richard M Cubbon","doi":"10.1093/cvr/cvaf055","DOIUrl":"https://doi.org/10.1093/cvr/cvaf055","url":null,"abstract":"<p><strong>Aims: </strong>Progressive deposition of cholesterol in the arterial wall characterizes atherosclerosis, which underpins most cases of myocardial infarction and stroke. Insulin-like growth factor-1 (IGF-1) is a hormone that regulates systemic growth and metabolism and possesses anti-atherosclerotic properties. We asked whether endothelial-restricted augmentation of IGF-1 signaling is sufficient to suppress atherogenesis.</p><p><strong>Methods and results: </strong>We generated mice with endothelial-restricted over-expression of human wildtype IGF-1R (hIGFREO/ApoE-/-) or a signaling defective K1003R mutant human IGF-1R (mIGFREO/ApoE-/-) and compared them to their respective ApoE-/- littermates. hIGFREO/ApoE-/- had less atherosclerosis, circulating leukocytes, arterial cholesterol uptake, and vascular leakage in multiple organs, whereas mIGFREO/ApoE-/- did not exhibit these phenomena. Overexpressing wildtype IGF-1R in human umbilical vein endothelial cells (HUVEC) altered the localization of tight junction proteins and reduced paracellular leakage across their monolayers, whilst overexpression of K1003R IGF-1R did not have these effects. Moreover, only overexpression of wildtype IGF-1R reduced HUVEC internalization of cholesterol-rich low density lipoprotein particles and increased their association of these particles with clathrin, but not caveolin-1, implicating it in vesicular uptake of lipoproteins. Endothelial overexpression of wildtype versus K1003R IGF-1R also reduced expression of YAP/TAZ target genes and nuclear localization of TAZ, which may be relevant to its impact on vascular barrier and atherogenesis.</p><p><strong>Conclusions: </strong>Endothelial IGF-1 signaling modulates both para- and trans-cellular vascular barrier function. Beyond reducing atherosclerosis, this could have relevance to many diseases associated with abnormal vascular permeability.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762736","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 paradigm shift in cardiovascular research - new method isolates intestinal interstitial fluid to understand gut microbiome and host cross talk.","authors":"Fadi J Charchar, Francine Z Marques","doi":"10.1093/cvr/cvaf047","DOIUrl":"https://doi.org/10.1093/cvr/cvaf047","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718070","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":"It takes more than omics to identify a cardioprotective mechanism.","authors":"Gerd Heusch, Petra Kleinbongard","doi":"10.1093/cvr/cvaf052","DOIUrl":"https://doi.org/10.1093/cvr/cvaf052","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699713","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":"Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis.","authors":"Marcin A Sowa, Carmen Hannemann, Ivan Pinos Cabezas, Elissa Ferreira, Bharti Biwas, Min Dai, Emma M Corr, Macintosh G Cornwell, Kamelia Drenkova, Angela H Lee, Tanya Spruill, Harmony R Reynolds, Judith Hochman, Kelly V Ruggles, Robert A Campbell, Coen van Solingen, Mark D Wright, Kathryn J Moore, Jeffrey S Berger, Tessa J Barrett","doi":"10.1093/cvr/cvaf051","DOIUrl":"https://doi.org/10.1093/cvr/cvaf051","url":null,"abstract":"<p><strong>Aim: </strong>To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37.</p><p><strong>Methods and results: </strong>To explore how stress contributes to platelet hyperreactivity, platelets were isolated from (1) mice that experienced chronic variable stress and stress-free controls (n=8/group) and (2) human subjects with self-reported high and no stress levels (n=18/group), followed by RNA-sequencing. By comparing mutually expressed transcripts, a subset of genes differentially expressed following psychosocial stress was identified in both human and mouse platelets. In both mice and humans, platelet CD37 positively associates with platelet aggregation responses that underlie thrombosis, with Cd37-/- platelets exhibiting impaired integrin αIIbβ3 signaling, characterized by reduced platelet fibrinogen spreading and decreased agonist-induced αIIbβ3 activation. Consistent with a role for CD37 in regulating platelet activation responses, chimeric mice that received Cd37-/- bone marrow experienced a significantly increased time to vessel occlusion in the carotid artery FeCl3 model compared to mice reconstituted with wild-type bone marrow. CD37 deficiency did not alter hemostasis, as platelet count, coagulation metrics, prothrombin time, and partial thromboplastin time did not differ in Cd37-/- mice relative to wild-type mice. Consistent with this, bleeding time did not differ between wild-type and Cd37-/- mice following tail tip transection.</p><p><strong>Conclusions: </strong>This study provides new insights into the platelet-associated mechanisms underlying stress-mediated thrombosis. Identifying CD37 as a novel regulator of platelet activation responses offers potential therapeutic targets for reducing the thrombotic risk associated with psychosocial stress. The findings also contribute to understanding how psychosocial stress accelerates thrombotic events and underscore the importance of platelet activation in this process.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699716","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":"From mice to humans: advancing the path to cardioprotection.","authors":"Lina Badimon, Gemma Vilahur, Guiomar Mendieta","doi":"10.1093/cvr/cvaf048","DOIUrl":"https://doi.org/10.1093/cvr/cvaf048","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669212","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":"Beneficial effects of vascular endothelial growth factor B gene transfer in the aged heart.","authors":"Nivethitha Manickam, Ibrahim Sultan, Josefine Panthel, Haris Kujundzic, Ariane Fischer, Katja Schmitz, Mariano Ruz Jurado, David Rodriguez Morales, David John, Simone-Franziska Glaser, Kathrin A Stilz, Pedro Felipe Malacarne, Ralf Peter Brandes, Thomas Braun, Carolin Lerchenmüller, Fynn Betge, Wesley T Abplanalp, Kari Alitalo, Stefanie Dimmeler, Julian U G Wagner","doi":"10.1093/cvr/cvaf046","DOIUrl":"https://doi.org/10.1093/cvr/cvaf046","url":null,"abstract":"<p><strong>Aim: </strong>Members of the VEGF family are crucial modulators of vascular and neural function. While VEGFA signaling has been shown to mitigate several aging-related cardiac phenotypes and prolong survival in aged mice, the role of VEGFB in cardiac aging remains underexplored. In this study, we identify a significant decline in Vegfb expression, particularly of its soluble isoform Vegfb186, in aged mouse and human hearts. To assess the therapeutic potential of VEGFB in aging-associated cardiac pathologies, we used AAV9-mediated gene transfer to overexpress Vegfb186 in 18-month-old male C57Bl/6J mice.</p><p><strong>Method and results: </strong>VEGFB is known to exhibit vascular and neuroprotective effects that we assessed in the ageing heart. In the aged heart, doses of Vegfb186 overexpression that had only a modest effect on the vascular endothelium prevented age-induced diastolic dysfunction and fibrosis. Vegfb186 treatment additionally restored sympathetic and sensory nerve fiber density and increased heart rate variability. Although Vegfb186 overexpression induced cardiac hypertrophy, our findings indicated that this hypertrophy was compensatory rather than pathological as Vegfb186 overexpression corrected the elevated cardiomyocyte length-to-width-ratio observed in aged hearts, a metric typically indicative of pathological remodeling. Cardiac single-nucleus RNA sequencing of the hearts and in vitro analysis of the cardiomyocytes indicated upregulation of the STAT3 signal transduction pathway as a potential contributor of VEGFB-induced cardiac hypertrophy.</p><p><strong>Conclusions: </strong>Our findings demonstrate that Vegfb186 overexpression partially reverses age-related cardiac pathologies such as diastolic dysfunction and fibrosis. This work highlights VEGFB as a potential therapeutic target for combating cardiac aging and its associated dysfunctions.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673282","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}