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Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1 (SVEP1) is a large secreted extracellular matrix glycoprotein, characterized by the presence of sushi, von Willebrand factor type A, EGF-like, and pentraxin domains[1][3]. SVEP1 functions as a physiological ligand for the orphan receptor PEAR1, triggering downstream AKT/mTOR signaling that regulates platelet activation and influences vascular cell function[2]. It plays critical roles in cell adhesion, endothelial development, vascular homeostasis, and the regulation of vasoconstriction through integrin interactions[3]. Genetic variants and circulating levels of SVEP1 are associated with increased risk of atherosclerosis, coronary artery disease, hypertension, type 2 diabetes, and other aging-related diseases[2]. SVEP1 is under investigation as a potential biomarker and as a target for novel therapies to address vascular and thrombotic diseases, though no approved drugs directly target it to date[2].
Ligand for the Platelet and Endothelial Aggregation Receptor 1 (PEAR1); binding promotes PEAR1 phosphorylation, leading to AKT/mTOR signaling activation in vascular cells and platelets, promoting platelet activation and vascular remodeling[2].
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