[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-462804-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-462804-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","cardio-vascular-extracellular-matrix-the-unmet-enigma","Cardio-Vascular Extracellular Matrix - The Unmet Enigma","","The cardiac extracellular matrix (ECM) functions as a dynamic, tissue-specific scaffold that is essential for cardiovascular development, homeostasis, and disease. Beyond passive structure, it actively regulates mechanical, electrical, and biochemical signaling, with composition changing from embryogenesis to adulthood. Pathological stimuli such as ischemia, overload, metabolic dysfunction, and aging disrupt ECM balance, promoting fibroblast activation, myofibroblast conversion, maladaptive collagen deposition, and myocardial fibrosis. These changes drive impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure. Imaging and biomarkers assist fibrosis assessment, while ECM-targeted therapies remain largely experimental.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/cardio-vascular-extracellular-matrix-the-unmet-enigma/462804/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/cardio-vascular-extracellular-matrix-the-unmet-enigma/462804.png","ImageObject",300,407,{"name":42,"@type":43},"Marglet","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How does the cardiac extracellular matrix (ECM) influence heart function?","Question",{"text":63,"@type":64},"The ECM is an active regulator of mechanical, electrical, and biochemical signaling. It supports cardiovascular processes such as cell migration, differentiation, and growth while coordinating homeostatic regulation.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which pathological stimuli can disrupt ECM homeostasis?",{"text":68,"@type":64},"ECM homeostasis can be disrupted by ischemia, pressure or volume overload, metabolic dysfunction, and aging. These factors contribute to fibroblast activation, myofibroblast transformation, and collagen dysregulation.",{"name":70,"@type":61,"acceptedAnswer":71},"What are the consequences of ECM remodeling for disease progression?",{"text":72,"@type":64},"Prolonged maladaptive remodeling leads to excessive fibrosis, causing harmful mechanical and electrical effects. This contributes to impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure in ischemic and non-ischemic cardiac diseases.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},462804,1790964314,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},2336477982702,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Review  \nCardio-Vascular Extracellular Matrix: The Unmet Enigma  \nIoannis Paraskevaidis 1,2, *, Elias Tsougos 2 and Christos Kourek 1, *  \nAcademic Editor: Claudia Kusmic  \nReceived: 9 December 2025  \nRevised: 29 December 2025  \nAccepted: 30 December 2025  \nPublished: 5 January 2026  \nCopyright: © 2026 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 Medical School of Athens, National and Kapodistrian University of Athens, 15772 Athens, Greece  \n2 Department of Cardiology, Hygeia Hospital, 15123 Athens, Greece; [tsougos@yahoo.com](tsougos@yahoo.com)  \n* Correspondence: [iparas@otenet.gr](iparas@otenet.gr) (I.P.); [chkourek@med.uoa.gr](chkourek@med.uoa.gr) (C.K.)  \nAbstract  \nThe cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age-and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations.  \nKeywords: heart failure; fibrosis; metalloproteinase; preserved ejection fraction; cardiovascular disease  \n1. Introduction  \nUntil a few years ago, it was believed that the extracellular matrix (ECM), a noncellular tissue, functioned merely as a static cardiovascular scaffold without particular properties and with questionable utility. However, over time, its role and multifunctional characteristics have emerged as a significant area of research. Indeed, it has been documented that the ECM is an active, tissue-specific entity influenced by several biochemical, mechanical, and hemodynamic forces and involved in many functions of the cardiovascular system, including cell migration, cell differentiation, tissue growth, fibrosis, etc. [1–4] . It is part of the homeostatic process and plays an important role in the genesis and progression of several cardiovascular diseases, since structural components of the ECM are involved in linking proteins with growth factors, in cell receptor–binding properties, and thus in maintaining both vascular and myocardial function. Additionally, it participates in dead-cell replacement mechanisms in various cardiovascular pathologies, including ischemic and non-ischemic cardiac diseases such as myocardial infarction and cardiomyopathies [5] .  \nGlycosaminoglycan (GAG) polymers such as hyaluronan (HA) and heparan sulfate are linked to proteoglycans and subsequently secreted. Sulphated proteoglycans (versican, aggrecan, etc.), forming aggregates with HA, have regulatory functions related to ECM hydration [6] . Heparan sulfate binds growth factors and cytokines, modifying their ac","cbCair8A6aBgfiiT","https://ap.wps.com/l/cbCair8A6aBgfiiT","pdf",2202233,25,"English","# Introduction\n## ECM as an active, tissue-specific scaffold\n## ECM composition and regulation by key molecular families\n## ECM remodeling, fibrosis, and cardiovascular outcomes","[{\"question\":\"How does the cardiac extracellular matrix (ECM) influence heart function?\",\"answer\":\"The ECM is an active regulator of mechanical, electrical, and biochemical signaling. It supports cardiovascular processes such as cell migration, differentiation, and growth while coordinating homeostatic regulation.\"},{\"question\":\"Which pathological stimuli can disrupt ECM homeostasis?\",\"answer\":\"ECM homeostasis can be disrupted by ischemia, pressure or volume overload, metabolic dysfunction, and aging. These factors contribute to fibroblast activation, myofibroblast transformation, and collagen dysregulation.\"},{\"question\":\"What are the consequences of ECM remodeling for disease progression?\",\"answer\":\"Prolonged maladaptive remodeling leads to excessive fibrosis, causing harmful mechanical and electrical effects. This contributes to impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure in ischemic and non-ischemic cardiac diseases.\"}]","Cardio-Vascular Extracellular Matrix - The Unmet Enigma | PDF",1790765268,63]