European Heart Journal最新文献

{"title":"Genetic testing in cardiomyopathies and new therapeutic target in cardiac remodelling.","authors":"Filippo Crea","doi":"10.1093/eurheartj/ehae890","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae890","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"15 1","pages":"333-336"},"PeriodicalIF":39.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991658","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":"Enhanced Parkin-mediated mitophagy mitigates adverse left ventricular remodelling after myocardial infarction: role of PR-364.","authors":"Lizhuo Ai, Juliana de Freitas Germano, Chengqun Huang, Marianne Aniag, Savannah Sawaged, Jon Sin, Reetu Thakur, Deepika Rai, Christopher Rainville, David E Sterner, Yang Song, Honit Piplani, Suresh Kumar, Tauseef R Butt, Robert M Mentzer, Aleksandr Stotland, Roberta A Gottlieb, Jennifer E Van Eyk","doi":"10.1093/eurheartj/ehae782","DOIUrl":"10.1093/eurheartj/ehae782","url":null,"abstract":"<p><strong>Background and aims: </strong>Almost 30% of survivors of myocardial infarction (MI) develop heart failure (HF), in part due to damage caused by the accumulation of dysfunctional mitochondria. Organelle quality control through Parkin-mediated mitochondrial autophagy (mitophagy) is known to play a role in mediating protection against HF damage post-ischaemic injury and remodelling of the subsequent deteriorated myocardium.</p><p><strong>Methods: </strong>This study has shown that a single i.p. dose (2 h post-MI) of the selective small molecule Parkin activator PR-364 reduced mortality, preserved cardiac ejection fraction, and mitigated the progression of HF. To reveal the mechanism of PR-364, a multi-omic strategy was deployed in combination with classical functional assays using in vivo MI and in vitro cardiomyocyte models.</p><p><strong>Results: </strong>In vitro cell data indicated that Parkin activation by PR-364 increased mitophagy and mitochondrial biogenesis, enhanced adenosine triphosphate production via improved citric acid cycle, altered accumulation of calcium localization to the mitochondria, and initiated translational reprogramming with increased expression of mitochondrial translational proteins. In mice, PR-364 administered post-MI resulted in widespread proteome changes, indicating an up-regulation of mitochondrial metabolism and mitochondrial translation in the surviving myocardium.</p><p><strong>Conclusions: </strong>This study demonstrates the therapeutic potential of targeting Parkin-mediated mitophagy using PR-364 to protect surviving cardiac tissue post-MI from progression to HF.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"380-393"},"PeriodicalIF":37.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727427","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":"Gold standard: Milton Packer honoured for pioneering work.","authors":"","doi":"10.1093/eurheartj/ehae723","DOIUrl":"10.1093/eurheartj/ehae723","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"337-338"},"PeriodicalIF":37.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799820","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":"Weekly Journal Scan: A CLEAR message questions the routine use of spironolactone in acute myocardial infarction.","authors":"Daniela Pedicino,Massimo Volpe","doi":"10.1093/eurheartj/ehae936","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae936","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"27 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991657","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":"Target 130/80: a future-focused initiative for hypertension management in Azerbaijan.","authors":"Ulvi Mirzoyev","doi":"10.1093/eurheartj/ehae749","DOIUrl":"10.1093/eurheartj/ehae749","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"341-343"},"PeriodicalIF":37.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799822","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":"Rising Stars: Sean Zheng.","authors":"","doi":"10.1093/eurheartj/ehae469","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae469","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":""},"PeriodicalIF":37.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002428","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":"Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes","authors":"Ana Carolina do A H Souza, Amelie S Troschel, Jan P Marquardt, Ibrahim Hadžić, Borek Foldyna, Filipe A Moura, Jon Hainer, Sanjay Divakaran, Ron Blankstein, Sharmila Dorbala, Marcelo F Di Carli, Hugo J W L Aerts, Michael T Lu, Florian J Fintelmann, Viviany R Taqueti","doi":"10.1093/eurheartj/ehae827","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae827","url":null,"abstract":"Background and Aims Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with body mass index (BMI), inflammation and risk of heart failure, myocardial infarction, and death. The relationship between SM quality, CMD, and cardiovascular outcomes is not known. Methods Consecutive patients (n = 669) undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion and preserved left ventricular ejection fraction were followed over a median of 6 years for major adverse cardiovascular events (MACEs), including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve was calculated as stress/rest myocardial blood flow. Subcutaneous adipose tissue (SAT), SM, and IMAT areas (cm2) were obtained from simultaneous positron emission tomography attenuation correction computed tomography using semi-automated segmentation at the 12th thoracic vertebra level. Results Median age was 63 years, 70% were female, and 46% were nonwhite. Nearly half of patients were obese (46%, BMI 30–61 kg/m2), and BMI correlated highly with SAT and IMAT (r = .84 and r = .71, respectively, P &amp;lt; .001) and moderately with SM (r = .52, P &amp;lt; .001). Decreased SM and increased IMAT, but not BMI or SAT, remained independently associated with decreased CFR (adjusted P = .03 and P = .04, respectively). In adjusted analyses, both lower CFR and higher IMAT were associated with increased MACE [hazard ratio 1.78 (95% confidence interval 1.23–2.58) per −1 U CFR and 1.53 (1.30–1.80) per +10 cm2 IMAT, adjusted P = .002 and P &amp;lt; .0001, respectively], while higher SM and SAT were protective [hazard ratio .89 (.81–.97) per +10 cm2 SM and .94 (.91–.98) per +10 cm2 SAT, adjusted P = .01 and .003, respectively]. Every 1% increase in fatty muscle fraction [IMAT/(SM + IMAT)] conferred an independent 2% increased odds of CMD [CFR &amp;lt;2, odds ratio 1.02 (1.01–1.04), adjusted P = .04] and a 7% increased risk of MACE [hazard ratio 1.07 (1.04–1.09), adjusted P &amp;lt; .001]. There was a significant interaction between CFR and IMAT, not BMI, such that patients with both CMD and fatty muscle demonstrated highest MACE risk (adjusted P = .02). Conclusions Increased intermuscular fat is associated with CMD and adverse cardiovascular outcomes independently of BMI and conventional risk factors. The presence of CMD and SM fat infiltration identified a novel at-risk cardiometabolic phenotype.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"11 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990318","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":"Obesity in familial hypercholesterolaemia: when precision medicine should meet precision population health.","authors":"Jean-Pierre Després","doi":"10.1093/eurheartj/ehae810","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae810","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"140 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991661","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":"Skeletal muscle adiposity in patients with impaired coronary flow reserve: risk marker, treatment target, or bystander?","authors":"Ranil de Silva,Kevin Cheng","doi":"10.1093/eurheartj/ehae909","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae909","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"10 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991715","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":"Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity","authors":"Yi You, Yu Tian, Rui Guo, Junfeng Shi, Kwang Joo Kwak, Yuhao Tong, Andreanne Poppy Estania, Wei-Hsiang Hsu, Yutong Liu, Shijun Hu, Jianhong Cao, Liqun Yang, Rui Bai, Pufeng Huang, Ly James Lee, Wen Jiang, Betty Y S Kim, Shuhong Ma, Xujie Liu, Zhenya Shen, Feng Lan, Patricia Kim Phuong Nguyen, Andrew S Lee","doi":"10.1093/eurheartj/ehae883","DOIUrl":"https://doi.org/10.1093/eurheartj/ehae883","url":null,"abstract":"Background and Aims Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims to demonstrate the pre-clinical efficacy and safety of extracellular vesicles (EVs) loaded with VEGF-A mRNA for the treatment of ischaemic vascular disease. Methods After encapsulation of full-length VEGF-A mRNA into fibroblast-derived EVs via cellular nanoporation (CNP), collected VEGF-A EVs were delivered into mouse models of ischaemic injury. Target tissue delivery was verified by in situ analysis of protein and gene expression. Functional rescue was confirmed by in vivo imaging and histology. The safety of single and serial delivery was demonstrated using immune-based assays. Results VEGF-A EVs were generated with high mRNA content using a CNP methodology. VEGF-A EV administration demonstrated expression of exogenous VEGF-A mRNA by in situ RNA hybridization and elevated protein expression by western blot, microscopy, and enzyme-linked immunosorbent assay. Mice treated with human VEGF-A EVs after femoral or coronary artery ligation exhibited heightened neovascularization in ischaemic tissues with increased arterial perfusion and improvement in left ventricular function, respectively. Serial delivery of VEGF-EVs in injured skin showed improved wound healing with repeat administration. Importantly, as compared with adeno-associated viral and lipid nanoparticle VEGF-A gene therapy modalities, murine VEGF-A EV delivery did not trigger innate or adaptive immune responses at the injection site or systemically. Conclusions This study demonstrated that VEGF-A EV therapy offers efficient, dose-dependent VEGF-A protein formation with low immunogenicity, resulting in new vessel formation in murine models of ischaemic vascular disease.","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":"18 1","pages":""},"PeriodicalIF":39.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991460","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}