Environmental Science & Technology Letters Environ.最新文献

{"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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The SEX-SHOCK score-the emperor's new clothes?","authors":"Karl-Patrik Kresoja, Maria Rubini Giménez, Holger Thiele","doi":"10.1093/eurheartj/ehae599","DOIUrl":"10.1093/eurheartj/ehae599","url":null,"abstract":"","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":" ","pages":"4579-4581"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Aesculapius project in Africa.","authors":"Roberto Ferrari, Alessandro Frigiola","doi":"10.1093/eurheartj/ehae500","DOIUrl":"10.1093/eurheartj/ehae500","url":null,"abstract":"","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":" ","pages":"4560-4561"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Was the embroidery needle truly fractured by the heart?","authors":"Yao Hu, Yurong Guo, Fuling Huang","doi":"10.1093/eurheartj/ehae634","DOIUrl":"10.1093/eurheartj/ehae634","url":null,"abstract":"","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":" ","pages":"4664"},"PeriodicalIF":37.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","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":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","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":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optical coherence tomography predictors of clinical outcomes after stent implantation: the ILUMIEN IV trial.","authors":"Ulf Landmesser, Ziad A Ali, Akiko Maehara, Mitsuaki Matsumura, Richard A Shlofmitz, Giulio Guagliumi, Matthew J Price, Jonathan M Hill, Takashi Akasaka, Francesco Prati, Hiram G Bezerra, William Wijns, David Leistner, Paolo Canova, Fernando Alfonso, Franco Fabbiocchi, Giuseppe Calligaris, Rohit M Oemrawsingh, Stephan Achenbach, Carlo Trani, Balbir Singh, Robert J McGreevy, Robert W McNutt, Shih-Wa Ying, Jana Buccola, Gregg W Stone","doi":"10.1093/eurheartj/ehae521","DOIUrl":"10.1093/eurheartj/ehae521","url":null,"abstract":"<p><strong>Background and aims: </strong>Observational registries have suggested that optical coherence tomography (OCT) imaging-derived parameters may predict adverse events after drug-eluting stent (DES) implantation. The present analysis sought to determine the OCT predictors of clinical outcomes from the large-scale ILUMIEN IV trial.</p><p><strong>Methods: </strong>ILUMIEN IV was a prospective, single-blind trial of 2487 patients with diabetes or high-risk lesions randomized to OCT-guided versus angiography-guided DES implantation. All patients underwent final OCT imaging (blinded in the angiography-guided arm). From more than 20 candidates, the independent OCT predictors of 2-year target lesion failure (TLF; the primary endpoint), cardiac death or target-vessel myocardial infarction (TV-MI), ischaemia-driven target lesion revascularization (ID-TLR), and stent thrombosis were analysed by multivariable Cox proportional hazard regression in single treated lesions.</p><p><strong>Results: </strong>A total of 2128 patients had a single treated lesion with core laboratory-analysed final OCT. The 2-year Kaplan-Meier rates of TLF, cardiac death or TV-MI, ID-TLR, and stent thrombosis were 6.3% (n = 130), 3.3% (n = 68), 4.3% (n = 87), and 0.9% (n = 18), respectively. The independent predictors of 2-year TLF were a smaller minimal stent area (per 1 mm2 increase: hazard ratio 0.76, 95% confidence interval 0.68-0.89, P < .0001) and proximal edge dissection (hazard ratio 1.77, 95% confidence interval 1.20-2.62, P = .004). The independent predictors of cardiac death or TV-MI were smaller minimal stent area and longer stent length; of ID-TLR were smaller intra-stent flow area and proximal edge dissection; and of stent thrombosis was smaller minimal stent expansion.</p><p><strong>Conclusions: </strong>In the ILUMIEN IV trial, the most important OCT-derived post-DES predictors of both safety and effectiveness outcomes were parameters related to stent area, expansion and flow, proximal edge dissection, and stent length.</p>","PeriodicalId":37,"journal":{"name":"Environmental Science & Technology Letters Environ.","volume":" ","pages":"4630-4643"},"PeriodicalIF":8.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142086037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}