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The O\u2010glycan structures of apo(a) subunit of Lp(a) serve as strong ligands of galectin\u20101, an O\u2010glycan binding pro\u2010angiogenic lectin abundantly expressed in placental vascular tissues. But the pathophysiological significance of apo(a)\u2010galectin\u20101 binding is not yet been revealed. Carbohydrate\u2010dependent binding of galectin\u20101 to another O\u2010glycoprotein, neuropilin\u20101 (NRP\u20101) on endothelial cells activates vascular endothelial growth factor receptor 2 (VEGFR2) and mitogen\u2010activated protein kinase (MAPK) signaling. Using apo(a), isolated from human plasma, we demonstrated the potential of the O\u2010glycan structures of apo(a) in Lp(a) to inhibit angiogenic properties such as proliferation, migration, and tube\u2010formation in human umbilical vein endothelial cells (HUVECs) as well as neovascularization in chick chorioallantoic membrane. Further, in vitro protein\u2010protein interaction studies have confirmed apo(a) as a superior ligand to NRP\u20101 for galectin\u20101 binding. We also demonstrated that the protein levels of galectin\u20101, NRP\u20101, VEGFR2, and downstream proteins in MAPK signaling were reduced in HUVECs in the presence of apo(a) with intact O\u2010glycan structures compared to that of de\u2010O\u2010glycosylated apo(a). In conclusion, our study shows that apo(a)\u2010linked O\u2010glycans prevent the binding of galectin\u20101 to NRP\u20101 leading to the inhibition of galectin\u20101\/neuropilin\u20101\/VEGFR2\/MAPK\u2010mediated angiogenic signaling pathway in endothelial cells. As higher plasma Lp(a) level in women is an independent risk factor for pre\u2010eclamsia, a pregnancy\u2010associated vascular complication, we propose that apo(a) O\u2010glycans\u2010mediated inhibition of the pro\u2010angiogenic activity of galectin\u20101 may be one of the underlying molecular mechanism of pathogenesis of Lp(a) in pre\u2010eclampsia.<\/jats:p>","DOI":"10.1096\/fj.202201001rr","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T13:05:31Z","timestamp":1676984731000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["O\u2010glycan structures in apo(a) subunit of human lipoprotein(a) suppresses the pro\u2010angiogenic activity of galectin\u20101 on human umbilical vein endothelial 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