{"title":"Weekly Journal Scan: A large Chinese SPRINT supports 'the lower, the better' blood pressure in hypertensive patients at high cardiovascular risk.","authors":"Rocco Vergallo, Massimo Volpe","doi":"10.1093/eurheartj/ehae531","DOIUrl":"10.1093/eurheartj/ehae531","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4665-4667"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125203","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}
Stefano Navarro, Ivan Talucci, Vanessa Göb, Stefanie Hartmann, Sarah Beck, Valerie Orth, Guido Stoll, Hans M Maric, David Stegner, Bernhard Nieswandt
{"title":"The humanized platelet glycoprotein VI Fab inhibitor EMA601 protects from arterial thrombosis and ischaemic stroke in mice.","authors":"Stefano Navarro, Ivan Talucci, Vanessa Göb, Stefanie Hartmann, Sarah Beck, Valerie Orth, Guido Stoll, Hans M Maric, David Stegner, Bernhard Nieswandt","doi":"10.1093/eurheartj/ehae482","DOIUrl":"10.1093/eurheartj/ehae482","url":null,"abstract":"<p><strong>Background and aims: </strong>Glycoprotein VI (GPVI) is a platelet collagen/fibrin(ogen) receptor and an emerging pharmacological target for the treatment of thrombotic and thrombo-inflammatory diseases, notably ischaemic stroke. A first anti-human GPVI (hGPVI) antibody Fab-fragment (ACT017/glenzocimab, KD: 4.1 nM) recently passed a clinical phase 1b/2a study in patients with acute ischaemic stroke and was found to be well tolerated, safe, and potentially beneficial. In this study, a novel humanized anti-GPVI antibody Fab-fragment (EMA601; KD: 0.195 nM) was developed that inhibits hGPVI function with very high potency in vitro and in vivo.</p><p><strong>Methods: </strong>Fab-fragments of the mouse anti-hGPVI IgG Emf6.1 were tested for functional GPVI inhibition in human platelets and in hGPVI expressing (hGP6tg/tg) mouse platelets. The in vivo effect of Emf6.1Fab was assessed in a tail bleeding assay, an arterial thrombosis model and the transient middle cerebral artery occlusion (tMCAO) model of ischaemic stroke. Using complementary-determining region grafting, a humanized version of Emf6.1Fab (EMA601) was generated. Emf6.1Fab/EMA601 interaction with hGPVI was mapped in array format and kinetics and quantified by bio-layer interferometry.</p><p><strong>Results: </strong>Emf6.1Fab (KD: 0.427 nM) blocked GPVI function in human and hGP6tg/tg mouse platelets in multiple assays in vitro at concentrations ≥5 µg/mL. Emf6.1Fab (4 mg/kg)-treated hGP6tg/tg mice showed potent hGPVI inhibition ex vivo and were profoundly protected from arterial thrombosis as well as from cerebral infarct growth after tMCAO, whereas tail-bleeding times remained unaffected. Emf6.1Fab binds to a so far undescribed membrane proximal epitope in GPVI. The humanized variant EMA601 displayed further increased affinity for hGPVI (KD: 0.195 nM) and fully inhibited the receptor at 0.5 µg/mL, corresponding to a >50-fold potency compared with ACT017.</p><p><strong>Conclusions: </strong>EMA601 is a conceptually novel and promising anti-platelet agent to efficiently prevent or treat arterial thrombosis and thrombo-inflammatory pathologies in humans at risk.</p>","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4582-4597"},"PeriodicalIF":8.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992259","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":"Concerns on 'Changes in frailty and incident cardiovascular disease in three prospective cohorts'.","authors":"Guo-Sheng Li, Hua-Fu Zhou","doi":"10.1093/eurheartj/ehae677","DOIUrl":"10.1093/eurheartj/ehae677","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4661"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461110","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}
Enrico Romagnoli, Mattia Lunardi, Francesco Burzotta
{"title":"Optical coherence tomography for optimal stent implantation: what to check?","authors":"Enrico Romagnoli, Mattia Lunardi, Francesco Burzotta","doi":"10.1093/eurheartj/ehae626","DOIUrl":"10.1093/eurheartj/ehae626","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4644-4646"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371302","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":"Refining the stratification of sudden cardiac death risk after myocardial infarction-beyond ejection fraction.","authors":"Ezimamaka C Ajufo, Usha B Tedrow","doi":"10.1093/eurheartj/ehae272","DOIUrl":"10.1093/eurheartj/ehae272","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4627-4629"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389077","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":"Correction to: A novel tool for arrhythmic risk stratification in desmoplakin gene variant carriers.","authors":"","doi":"10.1093/eurheartj/ehae501","DOIUrl":"10.1093/eurheartj/ehae501","url":null,"abstract":"","PeriodicalId":11976,"journal":{"name":"European Heart Journal","volume":" ","pages":"4597"},"PeriodicalIF":8.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859426","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}