Abstract :- Several investigations have shown that platelet endothelial aggregation receptor 1 (PEAR1) is critical in a number of physiological processes including phagocytosis, megakaryopoiesis, and platelet aggregation. However, few investigations have been conducted to elucidate the role of PEAR1 in endothelial cells, where it is most highly expressed. In this investigation, we utilized shRNA-mediated knockdown of PEAR1 in primary human umbilical vein endothelial cells (HUVECs) to determine the impact of PEAR1 on endothelial cell migration, adhesion, and proliferation. We extended our findings by examining the impact of the well-described PEAR1 variant, rs12041331, on HUVEC function, and evaluated the influence of this polymorphism on circulating endothelial biomarkers in 63 healthy subjects pre- and post-aspirin intervention (325 mg/day for 7 days). We observed that PEAR1 knockdown significantly reduced HUVEC migration, adhesion, and proliferation compared to control cells (P = 0.008, 0.02, and 0.009, respectively). Aspirin exposure largely abrogated the effect of PEAR1 knockdown on migration and adhesion (P = 0.19 and 0.24, respectively); however, proliferation remained significantly reduced compared to control cells (P = 0.01). rs12041331 did not significantly influence PEAR1 expression, and no significant difference in migration adhesion, or proliferation was observed by PEAR1 genotype pre- or post-aspirin administration. Furthermore, no genotypic differences in circulating endoglin, sVCAM-1, sICAM-1, or endothelin-1 levels were observed before or after aspirin treatment. Taken together, these results suggest that PEAR1 significantly impacts endothelial cell migration, adhesion, and proliferation, although further investigation is warranted to determine the influence of genetic variation and aspirin use on these traits.