Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL
Kyung-Sun Heo, Lan Phuong Phan, Nhi Thi Thao Le, Yujin Jin
{"title":"Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases","authors":"Kyung-Sun Heo,&nbsp;Lan Phuong Phan,&nbsp;Nhi Thi Thao Le,&nbsp;Yujin Jin","doi":"10.1007/s12272-025-01542-4","DOIUrl":null,"url":null,"abstract":"<div><p>Endothelial dysfunction plays a pivotal role in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, hypertension, heart failure, stroke, and peripheral artery disease. It disrupts vascular homeostasis, leading to reduced nitric oxide (NO) bioavailability, increased oxidative stress, and chronic inflammation, all of which collectively drive vascular damage, atherosclerotic plaque formation, and thrombosis. Additionally, shear stress-induced alterations in blood flow patterns, particularly disturbed flow (d-flow), aggravate endothelial dysfunction. Furthermore, the endothelial-to-mesenchymal transition (EndMT), a process in which endothelial cells acquire mesenchymal-like properties, contributes to vascular remodeling and accelerates CVD progression.</p><p>This review explores the significant role of epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs (ncRNAs), which serve as critical regulators of endothelial function in response to shear stress in endothelial dysfunction and the development of atherosclerosis. Furthermore, we discuss the pivotal role of endothelial dysfunction in cardiovascular and metabolic diseases, emphasizing the need for innovative therapeutic strategies beyond conventional treatments. In particular, we highlight the endothelial-protective mechanisms of emerging pharmacological agents, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, along with supporting clinical evidence demonstrating their efficacy in improving endothelial function and reducing cardiovascular risk.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"48 4","pages":"305 - 332"},"PeriodicalIF":6.9000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Pharmacal Research","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12272-025-01542-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Endothelial dysfunction plays a pivotal role in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, hypertension, heart failure, stroke, and peripheral artery disease. It disrupts vascular homeostasis, leading to reduced nitric oxide (NO) bioavailability, increased oxidative stress, and chronic inflammation, all of which collectively drive vascular damage, atherosclerotic plaque formation, and thrombosis. Additionally, shear stress-induced alterations in blood flow patterns, particularly disturbed flow (d-flow), aggravate endothelial dysfunction. Furthermore, the endothelial-to-mesenchymal transition (EndMT), a process in which endothelial cells acquire mesenchymal-like properties, contributes to vascular remodeling and accelerates CVD progression.

This review explores the significant role of epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs (ncRNAs), which serve as critical regulators of endothelial function in response to shear stress in endothelial dysfunction and the development of atherosclerosis. Furthermore, we discuss the pivotal role of endothelial dysfunction in cardiovascular and metabolic diseases, emphasizing the need for innovative therapeutic strategies beyond conventional treatments. In particular, we highlight the endothelial-protective mechanisms of emerging pharmacological agents, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors, along with supporting clinical evidence demonstrating their efficacy in improving endothelial function and reducing cardiovascular risk.

针对心血管疾病中内皮功能障碍的机制见解和新兴治疗策略
内皮功能障碍在动脉粥样硬化、高血压、心力衰竭、中风和外周动脉疾病等多种心血管疾病的发病机制中起着关键作用。它破坏血管稳态,导致一氧化氮(NO)生物利用度降低,氧化应激增加和慢性炎症,所有这些共同导致血管损伤,动脉粥样硬化斑块形成和血栓形成。此外,剪切应力引起的血流模式改变,特别是血流紊乱(d-flow),加重了内皮功能障碍。此外,内皮细胞向间充质转化(EndMT),即内皮细胞获得间充质样特性的过程,有助于血管重塑并加速心血管疾病的进展。这篇综述探讨了表观遗传机制的重要作用,如DNA甲基化、组蛋白修饰和非编码rna (ncRNAs),它们在内皮功能紊乱和动脉粥样硬化的发展中作为内皮功能响应剪切应力的关键调节因子。此外,我们讨论了内皮功能障碍在心血管和代谢疾病中的关键作用,强调了在传统治疗之外创新治疗策略的必要性。特别地,我们强调了新兴药理学药物的内皮保护机制,包括蛋白转化酶枯草杆菌素/酮素9型(PCSK9)抑制剂,胰高血糖素样肽-1受体激动剂(GLP-1RAs)和钠-葡萄糖共转运蛋白2 (SGLT2)抑制剂,以及支持临床证据证明其改善内皮功能和降低心血管风险的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信