{"title":"Delayed miR-199a Administration After Myocardial Infarction Precludes Pro-Regenerative Effects","authors":"Gia Burjanadze MD, PhD , Nikoloz Gorgodze MD, PhD , Giovanni Donato Aquaro MD , Khatia Gabisonia MD, PhD , Lucia Carlucci VD, PhD , Manendra Pachauri PhD , Federico Turreni MD , Ilaria Secco PhD , Fabio Bernini MS , Lorena Zentilin PhD , Mauro Giacca MD, PhD , Fabio A. Recchia MD, PhD","doi":"10.1016/j.jacbts.2024.12.014","DOIUrl":null,"url":null,"abstract":"<div><div>miR-199a carried by adeno-associated virus serotype 6 (AAV6) proved cardioreparative in a pig model when administered early after myocardial infarction (MI). To test whether the therapeutic efficacy of miR-199a is maintained when its administration is delayed, AAV6-miR-199a or a control AAV6 were injected 1 or 2 weeks after MI. Scar mass and cardiac contractile performance parameters were not significantly different between AAV6-miR-199a–treated and AAV6-control pigs. Nonetheless, most AAV6-miR-199a–treated pigs died from sudden death at 40 to 52 days after vector administration. For clinical translation, it appears mandatory to administer miR-199a early after MI and through modalities other than permanent expression from a viral vector.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 5","pages":"Pages 634-649"},"PeriodicalIF":8.4000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACC: Basic to Translational Science","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2452302X24004893","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
miR-199a carried by adeno-associated virus serotype 6 (AAV6) proved cardioreparative in a pig model when administered early after myocardial infarction (MI). To test whether the therapeutic efficacy of miR-199a is maintained when its administration is delayed, AAV6-miR-199a or a control AAV6 were injected 1 or 2 weeks after MI. Scar mass and cardiac contractile performance parameters were not significantly different between AAV6-miR-199a–treated and AAV6-control pigs. Nonetheless, most AAV6-miR-199a–treated pigs died from sudden death at 40 to 52 days after vector administration. For clinical translation, it appears mandatory to administer miR-199a early after MI and through modalities other than permanent expression from a viral vector.
在心肌梗死(MI)后早期给药的猪模型中,由腺相关病毒血清型6 (AAV6)携带的miR-199a证明具有心脏修复作用。为了检验延迟给药后miR-199a的治疗效果是否保持,在心肌梗死后1周或2周注射AAV6-miR-199a或对照AAV6。治疗AAV6-miR-199a的猪和对照AAV6-miR-199a的猪之间疤痕质量和心脏收缩性能参数无显著差异。尽管如此,大多数aav6 - mir -199a处理的猪在给药后40至52天猝死。对于临床转译,似乎必须在心肌梗死后早期通过病毒载体永久表达以外的方式给予miR-199a。
期刊介绍:
JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.