Cardiovascular Research最新文献

{"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}

{"title":"Immune cells and arrhythmias","authors":"Joshua A Keefe, Jian Wang, Jiangping Song, Li Ni, Xander Wehrens","doi":"10.1093/cvr/cvaf017","DOIUrl":"https://doi.org/10.1093/cvr/cvaf017","url":null,"abstract":"Cardiac arrhythmias are a significant cause of morbidity and mortality worldwide. Emerging evidence has demonstrated that resident and infiltrating cardiac immune cells play direct, mechanistic roles in arrhythmia onset and progression. In this review, we provide a comprehensive summary and expert commentary on the role of each immune cell subtype in the pathogenesis of atrial and ventricular arrhythmias.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"78 5 Pt 1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401241","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":"Emerging role of Cellular communication network factor 2 (CCN2) as a guardian of smooth muscle cell phenotype and vascular integrity.","authors":"J H Larsen, L B Steffensen","doi":"10.1093/cvr/cvaf015","DOIUrl":"https://doi.org/10.1093/cvr/cvaf015","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390376","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":"Glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist tirzepatide promotes branched chain amino acid catabolism to prevent myocardial infarction in non-diabetic mice.","authors":"Mengya Chen, Nan Zhao, Wenke Shi, Yun Xing, Shiqiang Liu, Xianxian Meng, Lanlan Li, Heng Zhang, Yanyan Meng, Saiyang Xie, Wei Deng","doi":"10.1093/cvr/cvaf005","DOIUrl":"https://doi.org/10.1093/cvr/cvaf005","url":null,"abstract":"<p><strong>Aims: </strong>A novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, tirzepatide (LY3298176, TZP), has been developed to treat Type 2 diabetes mellitus (T2DM). In ischaemic heart diseases, TZP is involved in cardiac metabolic processes. However, its efficacy and safety in treating heart failure (HF) following myocardial infarction (MI) remain uncertain.</p><p><strong>Methods and results: </strong>Herein, 12 week C57BL/6J mice were subjected to MI surgery, followed by administration of TZP. The effects of TZP on cardiac function and metabolism were thoroughly assessed by physiological, histological, and cellular analyses. Downstream effectors of TZP were screened through untargeted metabolomics analysis and molecular docking. Construct a lower branched chain amino acid (BCAA) diet model to determine whether TZP's cardioprotective effect is associated with reducing BCAA levels. Our results demonstrated that TZP reduced mortality following MI, decreased the infarct area, and attenuated cardiomyocyte necrosis. Pathological evaluation of cardiac tissues demonstrated increased fibrosis repair and decreased inflammatory infiltration. Mechanistically, untargeted metabolomics analysis uncovered a positive correlation between TZP and the BCAA catabolism pathway. The molecular docking verified that TZP could bind with branched-chain keto acid dehydrogenase E1 subunit α (BCKDHA). TZP reduced BCKDHA phosphorylation at S293, enhanced BCAA catabolism, and inhibited the activation of metabolism by activating rapamycin (mTOR) signalling pathway. Furthermore, mice fed a low-BCAA diet post-MI demonstrated reduced cardiomyocyte necrosis, increased fibrosis repair, and decreased inflammatory infiltration. These cardioprotective effects were further enhanced when used synergistically with TZP.</p><p><strong>Conclusion: </strong>Taken together, our findings provide new perspectives on the unrecognized role of TZP in cardiac protection. TZP enhanced BCAA catabolism and attenuated BCAA/mTOR signalling pathway in MI mice. Consequently, this study may present novel therapeutic options for patients with HF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390382","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":"Redirecting glucose into anabolic pathways participates in the protective effects of NRF2 activation in the heart under stress.","authors":"Thomas Eschenhagen","doi":"10.1093/cvr/cvaf003","DOIUrl":"https://doi.org/10.1093/cvr/cvaf003","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381698","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":"Interleukin-37 attenuates aortic valve lesions by inhibiting m6A-mediated IRAK-M degradation","authors":"Gaopeng Xian, Rong Huang, Dongtu Hu, Minhui Xu, Yangchao Chen, Hao Ren, Dingli Xu, Qingchun Zeng","doi":"10.1093/cvr/cvaf012","DOIUrl":"https://doi.org/10.1093/cvr/cvaf012","url":null,"abstract":"Aims Calcific aortic valve disease (CAVD) has become an increasingly important global medical problem without effective pharmacological intervention. Accumulating evidence indicates that aortic valve calcification is driven by inflammation. Interleukin-1 receptor-associated kinase M (IRAK-M) is a well-known negative regulator of inflammation, but its role in CAVD remains unclear. Methods and Results Here, we stimulated aortic valve interstitial cells (AVICs) with low-dose lipopolysaccharide (LPS) to mimic the inflammatory response in aortic valve calcification and observed the expression pattern of IRAK-M. Furthermore, we generated IRAK-M-/- mice to explore the effect of IRAK-M deficiency on the aortic valve in vivo. Additionally, overexpression and knockdown experiments were performed to verify the role of IRAK-M in AVICs. MeRIP‒qPCR was used to detect the N6-methyladenosine (m6A) level of IRAK-M, and recombinant interleukin (IL)-37-treated AVICs were used to determine the regulatory relationship between IL-37 and IRAK-M. We found that IRAK-M expression was upregulated in the early stages of inflammation as part of a negative feedback mechanism to modulate the immune response. However, persistent inflammation increased overall m6A levels, ultimately leading to reduced IRAK-M expression. In vivo, IRAK-M-/- mice exhibited a propensity for aortic valve thickening and calcification. Overexpression and knockdown experiments showed that IRAK-M inhibited inflammation and osteogenic responses in AVICs. In addition, IL-37 restored IRAK-M expression by inhibiting m6A-mediated IRAK-M degradation to suppress inflammation and aortic valve calcification. Conclusions Our findings confirm that inflammation and epigenetic modifications synergistically regulate IRAK-M expression. Moreover, IRAK-M represents a potential target for mitigating aortic valve calcification. Meanwhile, IL-37 exhibited inhibitory effects on CAVD development both in vivo and in vitro, giving us hope that CAVD can be treated with drugs rather than surgery.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"14 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258592","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":"Single cell RNA sequencing of hematopoietic cells in fresh and frozen human atheroma tissue.","authors":"Herra Ahmad, J K Gopakumar, Daniel C Nachun, Lisa Ma, Jessica D'Addabbo, Xianxi Huang, Tiffany Koyano, Jack Boyd, Y Joseph Woo, Robyn Fong, Oliver Aalami, Patricia K Nguyen, Siddhartha Jaiswal","doi":"10.1093/cvr/cvaf014","DOIUrl":"https://doi.org/10.1093/cvr/cvaf014","url":null,"abstract":"<p><strong>Aims: </strong>Single-cell RNA sequencing (scRNA-seq) is a powerful method for exploring the cellular heterogeneity within human atheroma but typically requires fresh tissue to preserve cell membrane integrity, limiting the feasibility of large-scale biobanking for later analysis. The aim of this study was to determine whether cryopreservation of fragile and necrotic atheroma tissue affects the viability and transcriptomic profiles of hematopoietic cells in subsequent scRNA-seq analysis, enabling the use of cryopreserved atheroma samples for future research.</p><p><strong>Methods and results: </strong>We performed scRNA-seq on five paired fresh and cryopreserved atheroma samples - three from coronary arteries and two from carotid arteries. Each sample was enzymatically digested, sorted for CD45+ hematopoietic cells, and processed using the 10X Genomics scRNA-seq workflow. Half of each sample was processed immediately, while the other half was cryopreserved in liquid nitrogen for an average of five weeks before thawing and processing. In carotid artery samples, we noted the absence of LYVE1+ macrophages, likely due to the loss of the adventitial layer during endarterectomy procedures. Our results indicated that cryopreservation modestly affected cellular integrity, leading to an increase in the relative abundance of mitochondrial RNA in frozen samples. Minimal differences were observed between fresh and cryopreserved samples in uniquely detected transcripts, cell clustering, or transcriptional profiles within hematopoietic populations.</p><p><strong>Conclusion(s): </strong>Our study demonstrates that cryopreserved human atheroma samples can be successfully profiled using scRNA-seq, with comparable transcriptomic data to that obtained from fresh samples. These findings suggest that cryopreservation is a viable method for biobanking atheroma tissues, facilitating large-scale studies without the need for immediate sample processing.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188419","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":"Cardioprotective effects of a 'twincretin' drug tirzepatide in heart failure following myocardial infarction.","authors":"Rui Shang, Brian Rodrigues","doi":"10.1093/cvr/cvaf006","DOIUrl":"https://doi.org/10.1093/cvr/cvaf006","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188417","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}