Integrin β3-mediated platelet extracellular vesicle adhesion facilitates vascular smooth muscle cell dysfunction in postinjury intimal hyperplasia

被引：0

作者：

Zhuang, Fei ^{[1
]}

Liu, Zhi-tong ^{[1
]}

Zhou, Guo ^{[1
]}

Liang, Feng ^{[1
]}

Wang, Ying-hua ^{[1
]}

Chen, Long ^{[1
]}

Zhang, Wei-feng ^{[1
]}

Shen, Ling-hong ^{[1
]}

Lu, Yan-qiao ^{[1
]}

Huo, Huan-huan ^{[1
]}

Shi, Xin ^{[1
]}

Fang, Liang ^{[2
]}

He, Ben ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Sch Med, Dept Cardiol, Shanghai 200030, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Sch Med, Dept Cardiac Surg, Shanghai 200030, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2025年 / 21卷 / 06期

基金：

中国国家自然科学基金;

关键词：

platelet-derived extracellular vesicles; intimal hyperplasia; vascular smooth muscle cell; SPP1; ITG beta 3; CALCIFICATION; MICROVESICLES; RECEPTOR; OSTEOPONTIN; EXOSOMES; PROTEIN;

D O I：

10.7150/ijbs.101391

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vascular smooth muscle cell (VSMC) dysfunction is a critical pathological process in postinjury intima hyperplasia. This process is driven by the adherence and accumulation of platelet-derived extracellular vesicles (PEVs) released from activated platelets to VSMCs at the site of injured intima. However, the precise mechanism remains unclear. Thus, the present study aimed to investigate how PEVs adhere to VSMCs and facilitate VSMC dysfunction in postinjury intimal hyperplasia. Morphological results confirmed that PEVs led to VSMC dysfunction and intimal hyperplasia. Integrated single-cell and proteomic analysis revealed that increased secreted phosphoprotein 1 (SPP1) expression in VSMCs played a central role in this process, possibly by mediating PEV adhesion to VSMCs and activating the focal adhesion kinase (FAK)/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) axis. In addition, integrin beta 3 (ITG(33, CD61) on PEVs, with increased expression under pathological conditions, was predicted to interact with SPP1. Co-immunoprecipitation (Co-IP) analysis further confirmed that ITG(33 interacted with SPP1, thereby activating the FAK/PI3K/AKT phosphorylation and promoting PEV adhesion. Of note, blocking ITG(33 expression on PEVs reduced PEV adhesion and intimal hyperplasia. Thus, ITG(33-SPP1-mediated PEV adhesion to VSMCs may be a novel mechanism in intimal hyperplasia, which proposed to be critical for vascular homeostasis.

引用

页码：2380 / 2395

页数：16

共 54 条

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