Cardiovascular Research最新文献

{"title":"Decoding ETV2 networks driving endothelial specification and cardiac repression.","authors":"Yena Oh,Sean M Wu","doi":"10.1093/cvr/cvaf161","DOIUrl":"https://doi.org/10.1093/cvr/cvaf161","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134071","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":"Defining HFpEF in rodents: a systematic review.","authors":"Yamen Adrah,Niklas Hegemann,David Faidel,Mariya M Kucherenko,Wolfgang M Kuebler,Gabriele G Schiattarella,Niklas Beyhoff,Jana Grune","doi":"10.1093/cvr/cvaf174","DOIUrl":"https://doi.org/10.1093/cvr/cvaf174","url":null,"abstract":"AIMSHeart failure (HF) with preserved ejection fraction (HFpEF) has become the most diagnosed HF subtype representing a major public health burden with poor clinical outcome. Available treatment options for HFpEF are limited, hence, more in-depth basic/translational research is needed to identify novel therapeutic targets. Preclinical investigations frequently rely on mice and rat models of HFpEF, yet their phenotypic accuracy is often not sufficiently verified. Here, we explore the extent to which rodent models labeled as 'HFpEF' reflect clinical diagnostic guidelines. We hypothesized that many basic/translational research articles use the term 'HFpEF' for rodent models, though the extent to which they demonstrate HFpEF signs and symptoms according to clinical definitions may be limited.METHODS AND RESULTSUsing the PubMed database, we identified N=475 studies using animal models of HFpEF that were published between 2008 and 2023. After exclusion of non-original research articles, articles using animal species other than mice or rats, and articles which did not claim the label 'HFpEF', N=407 studies remained and were evaluated, featuring a total of N=317 experimental groups labeled as 'HFpEF'. Based on predefined diagnostic clusters derived from the HF guidelines of the European Society of Cardiology, we found that 57% of these experimental groups (N=179) presented with the recommended level of evidence to support the use of the label 'HFpEF'. More recent publication dates and higher journal impact factors were positively associated with HFpEF probability.CONCLUSIONDespite many original articles labeling mouse and rat models as 'HFpEF', approximately two out of five studies fail to provide sufficient evidence to back this claim. Hence, caution is advised when interpreting mechanistic or interventional findings from studies involving rodent HFpEF models, and phenotypic documentation should be thoroughly assessed by readers and reviewers prior to drawing conclusions on the pathophysiology or treatment of HFpEF.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"18 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140322","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":"Oxidized LDL-induced FOXS1 mediates cholesterol transport dysfunction and inflammasome activation to drive aortic valve calcification.","authors":"Chen Jiang,Dingyi Yao,Qiang Shen,Rui Tian,Lin Fan,Qiang Zheng,Xingyu Qian,Zongtao Liu,Yuming Huang,Nianguo Dong","doi":"10.1093/cvr/cvaf159","DOIUrl":"https://doi.org/10.1093/cvr/cvaf159","url":null,"abstract":"AIMSCalcific aortic valve disease (CAVD) is becoming more prevalent with the population ageing; however, there is currently no medical therapy available. During early lipid deposition, low-density lipoprotein (LDL) mediates chronic inflammation and accelerates calcification progression. However, the mechanism still needs to be further explored.METHODS AND RESULTSThe study identified the transcription factor FOXS in human valvular interstitial cells (VICs) as a pivotal regulator in aortic valve calcification. Bulk RNA-seq and qRT-PCR analysis were conducted to establish that FOXS1 is induced by oxidized LDL (oxLDL) in VICs. To elucidate the role of FOXS1 in osteogenic differentiation, small interfering RNA and recombinant adenovirus were utilized to modulate FOXS1 expression in VICs. High-fat diet (HFD)-fed Apoe-/-Foxs1-/- mice served as an in vivo model to investigate the role of FOXS1 in aortic valve calcification. Analysis from bulk RNA-seq, qRT-PCR, and western blot indicated significant activation of FOXS1 by oxLDL in VICs, with silencing of FOXS1 inhibiting oxLDL-induced osteogenic differentiation. Deletion of FOXS1 markedly reduced aortic valve calcification in HFD-fed Apoe-/- mice, as shown by decreased calcium deposition in the aortic valve leaflets. RNA-seq and chromatin immunoprecipitation sequencing were performed to reveal the regulatory mechanisms of FOXS1, uncovering direct interactions with the promoter of BSCL2, which subsequently inhibits the expression of ABCA1 and ABCG1 via the PPARγ/LXRα axis. The study demonstrated that FOXS1 mediates VICs' cholesterol transport dysfunction through BSCL2, ABCA1, and ABCG1 using Bodipy-cholesterol and showed that intracellular cholesterol accumulation can activate the NLRP3 inflammasome, promoting osteogenic differentiation of VICs. Additionally, it was found that IMM-H007 and recombinant BSCL2 could reduce aortic valve calcification both in vitro and in vivo.CONCLUSIONWe identified that an oxLDL-induced transcription factor FOXS1 inhibits ABCA1 and ABCG1 expression via the BSCL2/PPARγ/LXRα axis and promotes cholesterol transport dysfunction and the activation of NLRP3 inflammasome in VICs, thereby accelerating the progression of CAVD.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"40 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127171","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":"Involvement of (trained) immunity in cardioprotection.","authors":"Gerd Heusch,Petra Kleinbongard","doi":"10.1093/cvr/cvaf170","DOIUrl":"https://doi.org/10.1093/cvr/cvaf170","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"61 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127172","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":"oxLDL-induced aortic valve inflammation and calcification - opportunities for clinical translation.","authors":"Yu-Jen Wang,Michael A Matter,Christian M Matter","doi":"10.1093/cvr/cvaf166","DOIUrl":"https://doi.org/10.1093/cvr/cvaf166","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"89 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117129","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":"Invasive validation of novel 1D models for computation of coronary fractional flow reserve.","authors":"Daniel J Taylor,Harry Saxton,Xu Xu,Eron Yones,Louise Aubiniere-Robb,Thilanka Adikari,Tom Newman,Marcel Van't Veer,Daniëlle C J Keulards,Pim Tonino,Rebecca Gosling,Krzysztof Czechowicz,Andrew Narracott,Rod Hose,Julian P Gunn,Ian Halliday,Paul D Morris","doi":"10.1093/cvr/cvaf168","DOIUrl":"https://doi.org/10.1093/cvr/cvaf168","url":null,"abstract":"INTRODUCTIONComputed virtual fractional flow reserve (vFFR), derived from invasive angiography, non-invasively quantifies coronary epicardial lesion physiology. Developments of 1D vFFR models have introduced methods of side-branch flow representation and reduced simulation time by several orders of magnitude versus 3D alternatives. However, no data exist reporting agreement and diagnostic accuracy in a matched cohort or giving comparison to established FFR alternatives.METHODS AND RESULTSWe used five 1D models, which differed in their side-branch flow representation, to compute vFFR in 104 arteries. The simplest model ignored side-branch flow, the second and third models used vessel anatomy to homogenously distribute side-branch flow and regionalise this to bifurcations respectively. The final two 1D models additionally used simulated pressure in the main vessel to modulate side-branch flow magnitude. To aid interpretability, diagnostic accuracy was also reported for 3D vFFR, visual assessment and resting invasive pressure assessment (Pd/Pa). Median FFR was 0.81 [0.73 - 0.88] and 46 (44%) lesions were haemodynamically significant. Optimal FFR agreement was achieved with the 1D model that regionalised side-branch flow to bifurcations (mean bias at diagnostic threshold -0.03, 95% agreement limits -0.23 to 0.20). Diagnostic accuracy did not differ significantly between the five 1D models, with area under the curve (AUC) values ranging 0.68 to 0.74. Diagnostic accuracy for 1D vFFR was superior to visual assessment, comparable to 3D vFFR and poorer than invasive resting pressure assessment.DISCUSSION1D models of vFFR facilitate rapid in-silico assessment of epicardial lesion severity. Inclusion of anatomical side branch flow mildly improved agreement, but the additional inclusion of simulated pressure was not beneficial. Agreement of 1D models was comparable to 3D simulations. However, current 1D models are not sufficiently accurate to suggest they may entirely replace wire-based assessment.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"9 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117134","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":"Impaired coronary flow reserve by hyperviscosity in a mouse model of non-light chain multiple myeloma – a mechanism of coronary flow impairment at the capillary level","authors":"Aleksandra Paterek, Filip Rolski, Mateusz Surzykiewicz, Zofia Pilch, Karol Czubak, Grażyna Hoser, Jakub Gołąb, Dominika Nowis, Tomasz Skirecki, Michał Mączewski","doi":"10.1093/cvr/cvaf164","DOIUrl":"https://doi.org/10.1093/cvr/cvaf164","url":null,"abstract":"Aims Multiple myeloma (MM) is associated with cardiovascular risk, although the exact underlying mechanisms are unknown. Here we tested the hypothesis that MM impairs coronary flow reserve due to increased blood viscosity caused by elevated monoclonal protein concentration. Methods and Results In a mouse Vĸ*MYC model of non-light chain MM recapitulating all aspects of human disease we showed that the disease progression was associated with progressive increase of blood and plasma viscosity. Using intravital microscopy imaging of ex vivo stained red blood cells we observed reduction of coronary flow reserve (CFR) in vivo with the CFR limiting site being coronary capillaries. This was further confirmed by similar coronary flow profile in mice with hyperviscosity induced by acute hyperlipidemia and disappearance of this MM-related CFR impairment in saline perfused ex vivo hearts. Of note, nitric oxide production in vivo was increased in the coronary circulation, especially at the capillary level, but the systemic concentration of nitric oxide metabolites was unchanged, again supporting the hypothesis that increased blood viscosity is the main culprit here. Moreover, MM progression was associated with progressive impairment of left and right ventricular function, but without histological signs of myocardial deterioration, hypertrophy or fibrosis. Conclusion Our study shows a potentially completely new mechanism of cardiovascular adverse effects caused by MM or more broadly by hyperviscosity syndromes, i.e., CFR impairment at the capillary level. Since capillaries, unlike larger vessels, cannot be recanalized or dilated, completely new preventive approaches are needed, such as agents affecting blood rheology.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"89 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089618","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 excitotoxicity in acute stroke: hope or hype.","authors":"Marco Micillo,Giuseppe Lembo","doi":"10.1093/cvr/cvaf154","DOIUrl":"https://doi.org/10.1093/cvr/cvaf154","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"38 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089768","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":"Protective effect of ursodeoxycholic acid upon the post-myocardial infarction heart.","authors":"Benedict Reilly-O'Donnell,Elisa Ferraro,Ryan Brody,Roman Tikhomirov,Catherine Mansfield,Catherine Williamson,Natalia Trayanova,Fu Siong Ng,Julia Gorelik","doi":"10.1093/cvr/cvaf133","DOIUrl":"https://doi.org/10.1093/cvr/cvaf133","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"68 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083529","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 new PCSK-9 monoclonal antibody for lowering LDL-cholesterol and lipoprotein(a) in Chinese patients with familial hypercholesterolaemia.","authors":"Seyed Saeed Tamehri Zadeh,Dick C Chan,Gerald F Watts","doi":"10.1093/cvr/cvaf160","DOIUrl":"https://doi.org/10.1093/cvr/cvaf160","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"35 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031716","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}