{"title":"Role of plasminogen activator inhibitor-1 (PAI-1) in age-related cardiovascular pathophysiology.","authors":"Alireza Khoddam, Douglas Vaughan, Lisa Wilsbacher","doi":"10.20517/jca.2024.38","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, and is driven by molecular and cellular mechanisms described in the hallmarks of aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, also mediates processes like vascular stiffness, cellular senescence, and immune evasion. This review highlights PAI-1's role in cardiovascular aging with a special emphasis on senescence, a key hallmark of aging. It further explores PAI-1's therapeutic potential, with a focus on its contribution to ECM remodeling, senescence signaling, and immune checkpoint regulation. Targeting PAI-1 could provide a promising strategy to mitigate age-related cardiovascular disease.</p>","PeriodicalId":75051,"journal":{"name":"The journal of cardiovascular aging","volume":"5 2","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12919670/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The journal of cardiovascular aging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.20517/jca.2024.38","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/21 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
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Abstract
Cardiovascular aging underpins the development of age-related diseases, including heart failure and vascular dysfunction, and is driven by molecular and cellular mechanisms described in the hallmarks of aging. Plasminogen activator inhibitor-1 (PAI-1), a key regulator of fibrinolysis, also mediates processes like vascular stiffness, cellular senescence, and immune evasion. This review highlights PAI-1's role in cardiovascular aging with a special emphasis on senescence, a key hallmark of aging. It further explores PAI-1's therapeutic potential, with a focus on its contribution to ECM remodeling, senescence signaling, and immune checkpoint regulation. Targeting PAI-1 could provide a promising strategy to mitigate age-related cardiovascular disease.
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