Thanga Yogeshwaran Gajendran , Nila Ganamurali , Sarvesh Sabarathinam
{"title":"7-Ketocholesterol: A pathogenic oxysterol in atherosclerosis and lysosomal storage disorders – Molecular insights and clinical implications","authors":"Thanga Yogeshwaran Gajendran , Nila Ganamurali , Sarvesh Sabarathinam","doi":"10.1016/j.jsbmb.2025.106797","DOIUrl":null,"url":null,"abstract":"<div><div>One important oxysterol produced by the autoxidation of cholesterol is 7-Ketocholesterol (7-KC), which plays a major role in both physiological and pathological processes. The pathogenic functions of 7-KC are reviewed in this study, with particular attention paid to its molecular processes and its participation in a number of diseases, such as lysosomal storage disorders (LSDs) and atherosclerosis. Through processes like oxidative stress, phospholipidosis, and lysosomal accumulation, 7-KC causes cytotoxicity, which in turn results in cell death. In atherosclerosis, it has a role in plaque instability, foam cell production, and endothelial dysfunction. Furthermore, 7-KC intensifies lysosomal dysfunction in LSDs, hastening the course of the illness. Additionally, 7-KC causes oxiapoptophagy, a kind of cell death marked by the co-occurrence of autophagy, apoptosis, and oxidative stress. By influencing inflammatory signalling, Reactive oxygen species (ROS) generation, and lipid peroxidation, 7-KC increases cellular damage and speeds up the aetiology of disease. This study clarifies how 7-KC contributes to endothelial dysfunction, atherosclerosis, and LSDs by highlighting its dual roles as a pathogenic molecule and a possible therapeutic target.</div></div>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":"252 ","pages":"Article 106797"},"PeriodicalIF":2.5000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Steroid Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960076025001256","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
One important oxysterol produced by the autoxidation of cholesterol is 7-Ketocholesterol (7-KC), which plays a major role in both physiological and pathological processes. The pathogenic functions of 7-KC are reviewed in this study, with particular attention paid to its molecular processes and its participation in a number of diseases, such as lysosomal storage disorders (LSDs) and atherosclerosis. Through processes like oxidative stress, phospholipidosis, and lysosomal accumulation, 7-KC causes cytotoxicity, which in turn results in cell death. In atherosclerosis, it has a role in plaque instability, foam cell production, and endothelial dysfunction. Furthermore, 7-KC intensifies lysosomal dysfunction in LSDs, hastening the course of the illness. Additionally, 7-KC causes oxiapoptophagy, a kind of cell death marked by the co-occurrence of autophagy, apoptosis, and oxidative stress. By influencing inflammatory signalling, Reactive oxygen species (ROS) generation, and lipid peroxidation, 7-KC increases cellular damage and speeds up the aetiology of disease. This study clarifies how 7-KC contributes to endothelial dysfunction, atherosclerosis, and LSDs by highlighting its dual roles as a pathogenic molecule and a possible therapeutic target.
期刊介绍:
The Journal of Steroid Biochemistry and Molecular Biology is devoted to new experimental and theoretical developments in areas related to steroids including vitamin D, lipids and their metabolomics. The Journal publishes a variety of contributions, including original articles, general and focused reviews, and rapid communications (brief articles of particular interest and clear novelty). Selected cutting-edge topics will be addressed in Special Issues managed by Guest Editors. Special Issues will contain both commissioned reviews and original research papers to provide comprehensive coverage of specific topics, and all submissions will undergo rigorous peer-review prior to publication.