htr2b介导的内皮保护：通过PI3K/AKT信号通路调节动脉粥样硬化中的铁凋亡

IF 3.4 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Therapeutics Pub Date : 2025-10-03 DOI:10.1155/cdr/7934590

Delin Li, Hui Li, Quanwei Zhao, Caiwei Gong, Long Chen, Chengzhu Xiong, Shaoliang Shen, Fujun Liao, Wupeng Liu, Danan Liu

{"title":"htr2b介导的内皮保护：通过PI3K/AKT信号通路调节动脉粥样硬化中的铁凋亡","authors":"Delin Li, Hui Li, Quanwei Zhao, Caiwei Gong, Long Chen, Chengzhu Xiong, Shaoliang Shen, Fujun Liao, Wupeng Liu, Danan Liu","doi":"10.1155/cdr/7934590","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>The current study is aimed at elucidating the mechanisms underlying the involvement of ferroptosis in atherosclerosis (AS) and exploring potential therapeutic targets.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Endothelial function and lipid peroxidation were assessed in vitro using HCAECs treated with OX-LDL. SLC7A11, GPX4, TfR1, and FTH1 were analyzed by western blot, respectively. Representative markers of ferroptosis including LDH, MDA, 4-HNE, GSH, and iron content were detected. HTR2B miRNA (OE-HTR2B) and controls (OE-NC, empty vector) were transfected. AS was induced in ApoE<sup>-/-</sup> mice through a high-fat diet. The effect of ferroptosis inhibition on atherosclerotic lesion development was evaluated by different inhibitor treatments.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>RNA-Seq analysis revealed dysregulated <i>HTR2B</i> expression in HCAECs exposed to OX-LDL, indicating its involvement in AS pathogenesis. OX-LDL exposure reduced cell viability and induced ferroptosis, characterized by decreased SLC7A11 and GPX4 expression and increased lipid peroxidation. Overexpression of <i>HTR2B</i> rescued cell viability, reduced Fe<sup>2+</sup> accumulation, and upregulated SLC7A11 and GPX4, suggesting a protective role against ferroptosis. Further, <i>HTR2B</i> regulated ferroptosis via the PI3K/AKT pathway, as evidenced by changes in pathway protein phosphorylation. By activating HTR2B with an agonist BW-723C86, we verified that <i>HTR2B</i> can inhibit ferroptosis through the PI3K/AKT pathway in an atherosclerotic mouse model.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>HTR2B suppressed ferroptosis by promoting the PI3K/AKT axis, enhanced cellular viability, and exhibited a protective role in AS.</p>\n </section>\n </div>","PeriodicalId":9582,"journal":{"name":"Cardiovascular Therapeutics","volume":"2025 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/7934590","citationCount":"0","resultStr":"{\"title\":\"HTR2B-Mediated Endothelial Protection: Modulating Ferroptosis via the PI3K/AKT Signaling Pathway in Atherosclerosis\",\"authors\":\"Delin Li, Hui Li, Quanwei Zhao, Caiwei Gong, Long Chen, Chengzhu Xiong, Shaoliang Shen, Fujun Liao, Wupeng Liu, Danan Liu\",\"doi\":\"10.1155/cdr/7934590\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>The current study is aimed at elucidating the mechanisms underlying the involvement of ferroptosis in atherosclerosis (AS) and exploring potential therapeutic targets.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Endothelial function and lipid peroxidation were assessed in vitro using HCAECs treated with OX-LDL. SLC7A11, GPX4, TfR1, and FTH1 were analyzed by western blot, respectively. Representative markers of ferroptosis including LDH, MDA, 4-HNE, GSH, and iron content were detected. HTR2B miRNA (OE-HTR2B) and controls (OE-NC, empty vector) were transfected. AS was induced in ApoE<sup>-/-</sup> mice through a high-fat diet. The effect of ferroptosis inhibition on atherosclerotic lesion development was evaluated by different inhibitor treatments.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>RNA-Seq analysis revealed dysregulated <i>HTR2B</i> expression in HCAECs exposed to OX-LDL, indicating its involvement in AS pathogenesis. OX-LDL exposure reduced cell viability and induced ferroptosis, characterized by decreased SLC7A11 and GPX4 expression and increased lipid peroxidation. Overexpression of <i>HTR2B</i> rescued cell viability, reduced Fe<sup>2+</sup> accumulation, and upregulated SLC7A11 and GPX4, suggesting a protective role against ferroptosis. Further, <i>HTR2B</i> regulated ferroptosis via the PI3K/AKT pathway, as evidenced by changes in pathway protein phosphorylation. By activating HTR2B with an agonist BW-723C86, we verified that <i>HTR2B</i> can inhibit ferroptosis through the PI3K/AKT pathway in an atherosclerotic mouse model.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>HTR2B suppressed ferroptosis by promoting the PI3K/AKT axis, enhanced cellular viability, and exhibited a protective role in AS.</p>\\n </section>\\n </div>\",\"PeriodicalId\":9582,\"journal\":{\"name\":\"Cardiovascular Therapeutics\",\"volume\":\"2025 1\",\"pages\":\"\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/cdr/7934590\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/cdr/7934590\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/cdr/7934590","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

摘要

目的本研究旨在阐明铁下垂参与动脉粥样硬化（AS）的机制并探索潜在的治疗靶点。方法采用OX-LDL处理hcaec，观察其内皮功能和脂质过氧化作用。western blot分析SLC7A11、GPX4、TfR1和FTH1。检测铁下垂的代表性标志物LDH、MDA、4-HNE、GSH、铁含量。转染HTR2B miRNA （OE-HTR2B）和对照组（OE-NC，空载体）。ApoE-/-小鼠通过高脂饮食诱导AS。通过不同的抑制剂治疗来评估铁下垂抑制对动脉粥样硬化病变发展的影响。结果RNA-Seq分析显示，暴露于OX-LDL的hcaec中HTR2B表达异常，提示其参与AS发病机制。OX-LDL暴露降低细胞活力并诱导铁下垂，其特征是SLC7A11和GPX4表达降低，脂质过氧化增加。HTR2B的过表达挽救了细胞活力，减少了Fe2+的积累，上调了SLC7A11和GPX4，提示其对铁凋亡具有保护作用。此外，HTR2B通过PI3K/AKT通路调节铁下垂，这可以通过通路蛋白磷酸化的变化来证明。通过使用激动剂BW-723C86激活HTR2B，我们验证了HTR2B可以通过PI3K/AKT途径抑制动脉粥样硬化小鼠模型中的铁下沉。结论HTR2B通过促进PI3K/AKT轴，增强细胞活力，抑制铁细胞凋亡，对AS具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

HTR2B-Mediated Endothelial Protection: Modulating Ferroptosis via the PI3K/AKT Signaling Pathway in Atherosclerosis

查看原文本刊更多论文

HTR2B-Mediated Endothelial Protection: Modulating Ferroptosis via the PI3K/AKT Signaling Pathway in Atherosclerosis

Objective

The current study is aimed at elucidating the mechanisms underlying the involvement of ferroptosis in atherosclerosis (AS) and exploring potential therapeutic targets.

Methods

Endothelial function and lipid peroxidation were assessed in vitro using HCAECs treated with OX-LDL. SLC7A11, GPX4, TfR1, and FTH1 were analyzed by western blot, respectively. Representative markers of ferroptosis including LDH, MDA, 4-HNE, GSH, and iron content were detected. HTR2B miRNA (OE-HTR2B) and controls (OE-NC, empty vector) were transfected. AS was induced in ApoE^-/- mice through a high-fat diet. The effect of ferroptosis inhibition on atherosclerotic lesion development was evaluated by different inhibitor treatments.

Results

RNA-Seq analysis revealed dysregulated HTR2B expression in HCAECs exposed to OX-LDL, indicating its involvement in AS pathogenesis. OX-LDL exposure reduced cell viability and induced ferroptosis, characterized by decreased SLC7A11 and GPX4 expression and increased lipid peroxidation. Overexpression of HTR2B rescued cell viability, reduced Fe²⁺ accumulation, and upregulated SLC7A11 and GPX4, suggesting a protective role against ferroptosis. Further, HTR2B regulated ferroptosis via the PI3K/AKT pathway, as evidenced by changes in pathway protein phosphorylation. By activating HTR2B with an agonist BW-723C86, we verified that HTR2B can inhibit ferroptosis through the PI3K/AKT pathway in an atherosclerotic mouse model.

Conclusion

HTR2B suppressed ferroptosis by promoting the PI3K/AKT axis, enhanced cellular viability, and exhibited a protective role in AS.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Cardiovascular Therapeutics 医学-心血管系统

CiteScore

5.60

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.