Cardiovascular Research最新文献

{"title":"Identifying optimal reference genes for qRT-PCR in human myocardial tissues.","authors":"Maria Camacho-Encina, Laura K Booth, Rachael Redgrave, Minna Honkanen-Scott, William E Scott, Carmen Martin-Ruiz, Guy MacGowan, Sarah Richardson, John Dark, Simon Tual-Chalot, Gavin D Richardson","doi":"10.1093/cvr/cvae194","DOIUrl":"https://doi.org/10.1093/cvr/cvae194","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139417","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":"Modulation of MMP9 and CXCR2/CXCL1/IL-8 axis in human abdominal aortic aneurysm tissues by ladarixin.","authors":"Maria Lombardi, Lucia Spartano, Sabrina Nicolo, Vincenzo Ardita, Roberto Chiesa, Andrea Aramini, Marcello Allegretti, Domenico Baccellieri, Lidia De Filippis, Chiara Foglieni","doi":"10.1093/cvr/cvae179","DOIUrl":"https://doi.org/10.1093/cvr/cvae179","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139418","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":"Influence of angiotensin II on the gut microbiome: modest effects in comparison to experimental factors.","authors":"Rikeish R Muralitharan, Michael E Nakai, Matthew Snelson, Tenghao Zheng, Evany Dinakis, Liang Xie, Hamdi Jama, Madeleine Paterson, Waled Shihata, Flavia Wassef, Antony Vinh, Grant R Drummond, David M Kaye, Charles R Mackay, Francine Z Marques","doi":"10.1093/cvr/cvae062","DOIUrl":"10.1093/cvr/cvae062","url":null,"abstract":"<p><strong>Aims: </strong>Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.</p><p><strong>Methods and results: </strong>We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).</p><p><strong>Conclusion: </strong>Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140189421","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":"Adenosine kinase inhibition protects mice from abdominal aortic aneurysm via epigenetic modulation of VSMC inflammation.","authors":"Jiean Xu, Zhiping Liu, Qiuhua Yang, Qian Ma, Yaqi Zhou, Yongfeng Cai, Dingwei Zhao, Guizhen Zhao, Tammy Lu, Kunfu Ouyang, Mei Hong, Ha Won Kim, Huidong Shi, Jifeng Zhang, David Fulton, Clint Miller, Rajeev Malhotra, Neal L Weintraub, Yuqing Huo","doi":"10.1093/cvr/cvae093","DOIUrl":"10.1093/cvr/cvae093","url":null,"abstract":"<p><strong>Aims: </strong>Abdominal aortic aneurysm (AAA) is a common, serious vascular disease with no effective pharmacological treatment. The nucleoside adenosine plays an important role in modulating vascular homeostasis, which prompted us to determine whether adenosine kinase (ADK), an adenosine metabolizing enzyme, modulates AAA formation via control of the intracellular adenosine level, and to investigate the underlying mechanisms.</p><p><strong>Methods and results: </strong>We used a combination of genetic and pharmacological approaches in murine models of AAA induced by calcium chloride (CaCl2) application or angiotensin II (Ang II) infusion to study the role of ADK in the development of AAA. In vitro functional assays were performed by knocking down ADK with adenovirus-short hairpin RNA in human vascular smooth muscle cells (VSMCs), and the molecular mechanisms underlying ADK function were investigated using RNA-sequencing, isotope tracing, and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The heterozygous deficiency of ADK protected mice from CaCl2- and Ang II-induced AAA formation. Moreover, specific knockout of ADK in VSMCs prevented Ang II-induced AAA formation, as evidenced by reduced aortic extracellular elastin fragmentation, neovascularization, and aortic inflammation. Mechanistically, ADK knockdown in VSMCs markedly suppressed the expression of inflammatory genes associated with AAA formation, and these effects were independent of adenosine receptors. The metabolic flux and ChIP-qPCR results showed that ADK knockdown in VSMCs decreased S-adenosylmethionine (SAM)-dependent transmethylation, thereby reducing H3K4me3 binding to the promoter regions of the genes that are associated with inflammation, angiogenesis, and extracellular elastin fragmentation. Furthermore, the ADK inhibitor ABT702 protected mice from CaCl2-induced aortic inflammation, extracellular elastin fragmentation, and AAA formation.</p><p><strong>Conclusion: </strong>Our findings reveal a novel role for ADK inhibition in attenuating AAA via epigenetic modulation of key inflammatory genes linked to AAA pathogenesis.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897395","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":"The significant impact of experimental variables on the gut microbiome.","authors":"Bhakti I Zakarauskas-Seth, Suphansa Sawamiphak","doi":"10.1093/cvr/cvae119","DOIUrl":"10.1093/cvr/cvae119","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236266","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":"Novel thrombolytic treatments of acute ischaemic stroke, choosing the right safety belt to drive this car.","authors":"Heleen M M van Beusekom, Meiqi Wang, Diederik W J Dippel","doi":"10.1093/cvr/cvae127","DOIUrl":"10.1093/cvr/cvae127","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261338","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 low bleeding risk thrombolytic agent: citPA5.","authors":"Shanli Chen, Sudan Fang, Yang Zhou, Zhiwei Huang, Shujuan Yu, Dan Chen, Zhiyou Wang, Yanyan Xu, Peiwen Liu, Yongkun Li, Wei Lin, Longguang Jiang, Cai Yuan, Mingdong Huang","doi":"10.1093/cvr/cvae060","DOIUrl":"10.1093/cvr/cvae060","url":null,"abstract":"<p><strong>Aims: </strong>Alteplase is a cornerstone thrombolytic agent in clinical practice but presents a potential bleeding risk. Stroke patients need pre-screening to exclude haemorrhagic stroke before using alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency.</p><p><strong>Methods and results: </strong>A clot lysis agent, named citPA5, is developed based on rtPA with point mutations to completely suppress its proteolytic activity in the absence of fibrin. In the presence of fibrin, citPA5 exhibited significantly higher fibrinolytic activity (a 15.8-fold increase of kcat/Km). Furthermore, citPA5 showed resistance to endogenous fibrinolysis inhibitor, PAI-1, resulting in enhanced potency. In a series of safety evaluation experiments, including thrombelastography assay, mice tail bleeding assay, and a murine intracerebral haemorrhage (ICH) model, citPA5 did not cause systemic bleeding or worsen ICH compared with alteplase. This highlights the low risk of bleeding associated with citPA5. Finally, we found that citPA5 effectively improved cerebral blood flow and reduced infarct volume in a carotid embolism-induced stroke model.</p><p><strong>Conclusion: </strong>This clot lysis agent, citPA5, not only exhibits a low risk of bleeding but also demonstrates highly effective thrombolysis capabilities. As a result, citPA5 shows great potential for administration prior to the classification of stroke types, making it possible for use in ambulances at the onset of stroke when symptoms are identified. The findings presented in this study also suggest that this strategy could be applied to develop a new generation of fibrinolytic drugs that offer greater safety and specificity in targeting fibrin.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305006","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 factor X stimulates atrial endothelial cells and tissues to promote remodelling responses through AT1R/NADPH oxidases/SGLT1/2.","authors":"Walaa Fakih, Ali Mroueh, Dal-Seong Gong, Shinnosuke Kikuchi, Michael Paul Pieper, Michel Kindo, Jean-Philippe Mazzucottelli, Arnaud Mommerot, Mohamad Kanso, Patrick Ohlmann, Olivier Morel, Valérie Schini-Kerth, Laurence Jesel","doi":"10.1093/cvr/cvae101","DOIUrl":"10.1093/cvr/cvae101","url":null,"abstract":"<p><strong>Aims: </strong>Atrial fibrillation (AF), the most common cardiac arrhythmia favouring ischemic stroke and heart failure involves left atrial remodelling, fibrosis and a complex interplay between cardiovascular risk factors. This study examined whether activated factor X (FXa) induces pro-remodelling and pro-fibrotic responses in atrial endothelial cells (AECs) and human atrial tissues and determined the underlying mechanisms.</p><p><strong>Methods and results: </strong>AECs collected from porcine hearts and human right atrial appendages (RAA) from patients undergoing heart surgery. Protein expression levels were assessed by Western blot and immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and NO using fluorescent probes, thrombin and angiotensin II generation by specific assays, fibrosis by Sirius red staining and senescence by senescence-associated beta-galactosidase (SA-β-gal) activity. In AECs, FXa increased ROS formation, senescence (SA-β-gal activity, p53, p21), angiotensin II generation and the expression of pro-inflammatory (VCAM-1, MCP-1), pro-thrombotic (tissue factor), pro-fibrotic (TGF-β and collagen-1/3a) and pro-remodelling (MMP-2/9) markers whereas eNOS levels and NO formation were reduced. These effects were prevented by inhibitors of FXa but not thrombin, protease-activated receptors antagonists (PAR-1/2) and inhibitors of NADPH oxidases, ACE, AT1R, SGLT1/SGLT2. FXa also increased expression levels of ACE1, AT1R, SGLT1/2 proteins which were prevented by SGLT1/2 inhibitors. Human RAA showed tissue factor mRNA levels that correlated with markers of endothelial activation, pro-remodelling and pro-fibrotic responses and SGLT1/2 mRNA levels. They also showed protein expression levels of ACE1, AT1R, p22phox, SGLT1/2, and immunofluorescence signals of nitrotyrosine and SGLT1/2 colocalized with those of CD31. FXa increased oxidative stress levels which were prevented by inhibitors of the AT1R/NADPH oxidases/SGLT1/2 pathway.</p><p><strong>Conclusion: </strong>FXa promotes oxidative stress triggering premature endothelial senescence and dysfunction associated with pro-thrombotic, pro-remodelling and pro-fibrotic responses in AECs and human RAA involving the AT1R/NADPH oxidases/SGLT1/2 pro-oxidant pathway. Targeting this pathway may be of interest to prevent atrial remodelling and the progression of atrial fibrillation substrate.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921091","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":"Retraction of: Transcription factor Krüppel-like factor 2 plays a vital role in endothelial colony forming cells differentiation.","authors":"","doi":"10.1093/cvr/cvae048","DOIUrl":"10.1093/cvr/cvae048","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305008","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":"The ketogenic diet is unable to improve cardiac function in ischaemic heart failure: an unexpected result?","authors":"Carolina Magdalen Greco, Enzo Nisoli","doi":"10.1093/cvr/cvae126","DOIUrl":"10.1093/cvr/cvae126","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261348","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}