Rivaroxaban as a Protector of Oxidative Stress-Induced Vascular Endothelial Glycocalyx Damage via the IQGAP1/PAR1-2/PI3K/Akt Pathway

被引：1

作者：

Kitasato, Lisa ^{[1
]}

Yamaoka-Tojo, Minako ^{[2
]}

Iwaya, Toshiyuki ^{[1
,3
]}

Murayama, Yusuke ^{[1
,3
]}

Ikeda, Yuki ^{[1
]}

Hashikata, Takehiro ^{[1
]}

Oikawa, Jun ^{[4
]}

Suzuki, Machika ^{[1
]}

Misawa, Nonoka ^{[5
]}

Kawashima, Rei ^{[5
]}

Ogawa, Fumihiro ^{[6
]}

Ako, Junya ^{[1
]}

机构：

[1] Kitasato Univ, Sch Med, Dept Cardiovasc Med, Sagamihara, Japan

[2] Kitasato Univ, Sch Allied Hlth Sci, Dept Rehabil, Sagamihara, Japan

[3] Kitasato Univ, Grad Sch Med Sci, Sagamihara, Japan

[4] Kitasato Univ, Dept Kitasato Clin Res Ctr, Sch Med, Sagamihara, Japan

[5] Kitasato Univ, Sch Allied Hlth Sci, Dept Regulat Biochem, Sagamihara, Japan

[6] Yokohama City Univ, Sch Med, Dept Emergency Med, Yokohama, Japan

来源：

JOURNAL OF VASCULAR RESEARCH | 2025年 / 62卷 / 01期

基金：

日本学术振兴会;

关键词：

Vascular endothelial glycocalyx; Endothelial cells; IQGAP1; Rivaroxaban; Oxidative stress; PI3K/Akt pathway; FACTOR-XA; CELL PROLIFERATION; IQGAP1; PROTEIN; IN-VIVO; ACTIVATION; BARRIER; PERMEABILITY; EXPRESSION; BINDING; INFLAMMATION;

D O I：

10.1159/000542419

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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 factor X inhibitor, on the glycocalyx under oxidative stress condition. Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells 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.

引用

页码：22 / 36

页数：15

共 84 条

[1] Syndecans in wound healing, inflammation and vascular biology [J].