Lisa Kitasato, Minako Yamaoka-Tojo, Toshiyuki Iwaya, Yusuke Murayama, Yuki Ikeda, Takehiro Hashikata, Jun Oikawa, Machika Suzuki, Nonoka Misawa, Rei Kawashima, Fumihiro Ogawa, Junya Ako
{"title":"利伐沙班通过 IQGAP1/PAR1-2/PI3K/Akt 通路保护氧化应激诱导的血管内皮糖萼损伤","authors":"Lisa Kitasato, Minako Yamaoka-Tojo, Toshiyuki Iwaya, Yusuke Murayama, Yuki Ikeda, Takehiro Hashikata, Jun Oikawa, Machika Suzuki, Nonoka Misawa, Rei Kawashima, Fumihiro Ogawa, Junya Ako","doi":"10.1159/000542419","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition.</p><p><strong>Methods: </strong>We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress.</p><p><strong>Results: </strong>Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.</p><p><strong>Conclusion: </strong>We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.</p>","PeriodicalId":17530,"journal":{"name":"Journal of Vascular Research","volume":" ","pages":"1-24"},"PeriodicalIF":1.8000,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway.\",\"authors\":\"Lisa Kitasato, Minako Yamaoka-Tojo, Toshiyuki Iwaya, Yusuke Murayama, Yuki Ikeda, Takehiro Hashikata, Jun Oikawa, Machika Suzuki, Nonoka Misawa, Rei Kawashima, Fumihiro Ogawa, Junya Ako\",\"doi\":\"10.1159/000542419\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition.</p><p><strong>Methods: </strong>We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress.</p><p><strong>Results: </strong>Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.</p><p><strong>Conclusion: </strong>We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.</p>\",\"PeriodicalId\":17530,\"journal\":{\"name\":\"Journal of Vascular Research\",\"volume\":\" \",\"pages\":\"1-24\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2024-11-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Vascular Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000542419\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Vascular Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000542419","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway.
Introduction: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition.
Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress.
Results: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx.
Conclusion: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.
期刊介绍：
The ''Journal of Vascular Research'' publishes original articles and reviews of scientific excellence in vascular and microvascular biology, physiology and pathophysiology. The scope of the journal covers a broad spectrum of vascular and lymphatic research, including vascular structure, vascular function, haemodynamics, mechanics, cell signalling, intercellular communication, growth and differentiation. JVR''s ''Vascular Update'' series regularly presents state-of-the-art reviews on hot topics in vascular biology. Manuscript processing times are, consistent with stringent review, kept as short as possible due to electronic submission. All articles are published online first, ensuring rapid publication. The ''Journal of Vascular Research'' is the official journal of the European Society for Microcirculation. A biennial prize is awarded to the authors of the best paper published in the journal over the previous two years, thus encouraging young scientists working in the exciting field of vascular biology to publish their findings.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
