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 (ITGβ3, CD61) on PEVs, with increased expression under pathological conditions, was predicted to interact with SPP1. Co-immunoprecipitation (Co-IP) analysis further confirmed that ITGβ3 interacted with SPP1, thereby activating the FAK/PI3K/AKT phosphorylation and promoting PEV adhesion. Of note, blocking ITGβ3 expression on PEVs reduced PEV adhesion and intimal hyperplasia. Thus, ITGβ3-SPP1-mediated PEV adhesion to VSMCs may be a novel mechanism in intimal hyperplasia, which proposed to be critical for vascular homeostasis.
Keywords: ITGβ3; SPP1; intimal hyperplasia; platelet-derived extracellular vesicles; vascular smooth muscle cell.
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