Platelet endothelial aggregation receptor 1 (PEAR1)

Platelet endothelial aggregation receptor 1 (PEAR1) is a type I transmembrane receptor containing multiple EGF-like domains, most highly expressed in platelets, endothelial cells, and fibroblasts[1][3]. PEAR1 mediates secondary signaling during platelet aggregation, particularly downstream of integrin αIIbβ3, and is phosphorylated upon platelet-platelet contact[3]. It acts both in platelets (modulating aggregation and response to antiplatelet drugs such as aspirin and thienopyridines) and endothelial cells (regulating migration, angiogenesis, and vascular homeostasis)[1][2][5]. PEAR1's signaling pathways include PI3K/Akt and likely interact with SH2 domain-containing adaptors[1][2][3]. It is implicated in a range of vascular conditions, including cardiovascular disease, pulmonary fibrosis (via fibroblast regulation), and wound healing[1][2][5]. Genetic variants, notably rs12041331, serve as pharmacogenomic biomarkers for antiplatelet response and cardiovascular risk[1]. Multiple endogenous and exogenous ligands have been reported, including SVEP1, FcεR1α, dextran sulfate, and fucoidan[2][5]. Targeting the PEAR1 pathway therapeutically raises concerns given its pleiotropic roles in vascular integrity and repair[1][5].

Other names

PEAR1MEGF12JEDIFLJ00193Multiple EGF-like domains protein 12hPEAR1Multiple epidermal growth factor-like domains protein 12

Drugs such as aspirin, prasugrel, and clopidogrel modulate platelet aggregation partly in relation to PEAR1 genotype. Eptifibatide blocks integrin αIIbβ3-mediated aggregation and subsequent PEAR1 phosphorylation, interrupting aggregation-induced signaling. Modulation of PEAR1-related signaling (e.g., AKT/mTOR pathway) may regulate platelet and endothelial activity.