[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-461883-105":59,"doc-detail-461883-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","modified-mrna-based-therapeutic-strategies-for-myocardial-ischemia-reperfusion-injury","Modified mRNA-Based Therapeutic Strategies for Myocardial Ischemia - Reperfusion Injury","","Ischemic heart disease is a leading cause of cardiovascular morbidity and mortality worldwide, and revascularization can restore blood flow while also triggering myocardial ischemia–reperfusion injury (MIRI). MIRI pathogenesis reflects interacting mechanisms including oxidative stress, intracellular calcium overload, inflammatory activation, apoptosis, autophagy, and microvascular endothelial dysfunction. Modified RNA (modRNA) is reviewed as a therapeutic approach with improved molecular stability, reduced immunogenicity, and controllable transient protein expression. Optimized modRNA delivery systems support localized expression of antioxidant, anti-apoptotic, and pro-angiogenic genes, while remaining clinical translation challenges include targeted delivery and balancing transfection efficiency with cytotoxicity.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/modified-mrna-based-therapeutic-strategies-for-myocardial-ischemia-reperfusion-injury/461883/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/modified-mrna-based-therapeutic-strategies-for-myocardial-ischemia-reperfusion-injury/461883.png","ImageObject",300,407,{"name":92,"@type":93},"Eliana","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is myocardial ischemia–reperfusion injury (MIRI) and why does it occur after revascularization?","Question",{"text":113,"@type":114},"MIRI is the cardiac dysfunction caused when blood flow restoration triggers additional damage to cardiomyocytes. Revascularization rescues ischemic tissue but can induce cell death and related pathological processes.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which molecular mechanisms are involved in the pathogenesis of MIRI?",{"text":118,"@type":114},"The review describes multiple interrelated mechanisms, including oxidative stress with ROS/RNS, intracellular calcium dysregulation, microvascular and endothelial dysfunction, mitochondrial dysfunction, inflammatory activation, apoptosis, and autophagy deregulation.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is modified mRNA (modRNA) considered promising for MIRI treatment, and what challenges remain?",{"text":122,"@type":114},"modRNA is highlighted for enhanced stability, reduced immunogenicity, and controllable transient protein expression at injury sites. Translation challenges include delivery system targeting and achieving sufficient transfection efficiency while limiting cytotoxicity.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},461883,1790816817,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},4398048949847,"https://ap-avatar.wpscdn.com/avatar/400002536579ef2da7f?_k=1778318612642679267","Review  \nModified mRNA-Based Therapeutic Strategies for Myocardial Ischemia–Reperfusion Injury  \nTing Cai 1 and Xiang-Qun Yang 2, *  \nReceived: 4 November 2025  \nRevised: 4 December 2025  \nAccepted: 6 December 2025  \nPublished: 20 December 2025  \nCopyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 School of Gongli Hospital Medical Technology, University of Shanghai for Science and Technology, Shanghai 200093, China  \n2 Department of Human Anatomy, Naval Medical University, Shanghai 200433, China  \n* [Correspondence: yangxq_sh@126.com](Correspondence: yangxq_sh@126.com)  \nAbstract  \nIschemic heart disease (IHD), the leading causes of cardiovascular morbidity and mortality worldwide, is currently treated though revascularization strategies such as pharmacological thrombolysis, coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) . However, the restoration of blood flow often induces cardiac dysfunction, known as myocardial ischemia–reperfusion injury (MIRI) . The pathogenesis of MIRI involves a complex, multifactorial process characterized by the interplay of diverse pathophysiological mechanisms, including oxidative stress, intracellular calcium overload, inflammatory cascade activation, apoptosis, autophagy, and microvascular endothelial dysfunction. In recent years, modified RNA (modRNA) technology has emerged as a novel therapeutic strategy for MIRI due to its enhanced molecular stability, reduced immunogenicity, and controllable transient protein expression. Studies have demonstrated that optimized modRNA delivery systems enable efficient, localized expression of therapeutic genes (e.g., antioxidant, anti-apoptotic, and pro-angiogenic factors) at injury sites, significantly mitigating MIRI-associated pathological damage. Nevertheless, significant challenges remain in clinical translation, such as delivery system targeting, transfection efficiency and cytotoxicity. This review focuses on recent advances in the development and application of modRNA-based delivery systems for MIRI treatment. Understanding the molecular mechanisms of MIRI and the structural characteristics and application of modRNA may encourage researchers to explore promising therapeutic modalities for addressing reperfusion-related cardiac injury.  \nKeywords: modRNA; myocardial ischemia–reperfusion injury; gene therapy; cardiovascular diseases; nano delivery  \n1. Introduction  \nIschemic heart disease (IHD) remains one of the leading causes of cardiovascular mortality worldwide [1,2] . Pathologically, IHD is characterized by coronary artery occlusion, leading to cellular metabolic dysfunction, ischemic myocardial necrosis, and subsequent cardiac dysfunction of varying severity [3] . In current clinical treatment strategies, revascularization serves as the cornerstone for improving myocardial ischemia, primarily including: pharmacological thrombolysis, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) [3,4] . These treatment strategies exhibit substantial effectiveness in rescuing at-risk myocardial tissue and enhancing patient prognosis by promptly reestablishing blood perfusion to ischemic heart muscle.  \nThe restoration of blood flow, nevertheless, can induce cardiomyocyte death, clinically recognized as myocardial ischemia–reperfusion injury (MIRI) [5] . The pathogenesis of myocardial ischemia/reperfusion (I/R) injury involves multi-level pathophysiological processes, primarily including the following interrelated mechanisms: excessive production of reactive oxygen/nitrogen species (ROS/RNS); dysregulation of intracellular calcium homeostasis; microvascular and endothelial dysfunction; metabolic disturbances including adenosine triphosphate (ATP) depletion and hydrogen ion accumulation-induced acidosis; activation of innate immune compon","cbCailDzvb0LngV9","https://ap.wps.com/l/cbCailDzvb0LngV9","pdf",1751314,21,"English","# Introduction\n# Abstract\n# Keywords","[{\"question\":\"What is myocardial ischemia–reperfusion injury (MIRI) and why does it occur after revascularization?\",\"answer\":\"MIRI is the cardiac dysfunction caused when blood flow restoration triggers additional damage to cardiomyocytes. Revascularization rescues ischemic tissue but can induce cell death and related pathological processes.\"},{\"question\":\"Which molecular mechanisms are involved in the pathogenesis of MIRI?\",\"answer\":\"The review describes multiple interrelated mechanisms, including oxidative stress with ROS/RNS, intracellular calcium dysregulation, microvascular and endothelial dysfunction, mitochondrial dysfunction, inflammatory activation, apoptosis, and autophagy deregulation.\"},{\"question\":\"Why is modified mRNA (modRNA) considered promising for MIRI treatment, and what challenges remain?\",\"answer\":\"modRNA is highlighted for enhanced stability, reduced immunogenicity, and controllable transient protein expression at injury sites. Translation challenges include delivery system targeting and achieving sufficient transfection efficiency while limiting cytotoxicity.\"}]","Modified mRNA-Based Therapeutic Strategies for Myocardial Ischemia - Reperfusion Injury | PDF",1790762666,53]