{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:13:22Z","timestamp":1780492402531,"version":"3.54.1"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP). Nanoparticles containing a plasmid expressing the low-density lipoprotein receptor extracellular domain nanoparticle were used as negative control. MTT, modified Boyden chamber, and Matrigel (\u2122) assays were used to evaluate the inhibitory effect of VLN-NP on Wnt3a-stimulated endothelial cell proliferation, migration, and tube formation.\n              <jats:italic>Vldlr<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice, oxygen-induced retinopathy, and alkali burn\u2013induced corneal neovascularization models were used to evaluate the effect of VLN-NP on ocular neovascularization. Wnt reporter mice (BAT-gal), Western blotting, and luciferase assay were used to evaluate Wnt pathway activity. Our results showed that VLN-NP specifically inhibited Wnt3a-induced endothelial cell proliferation, migration, and tube formation. Intravitreal injection of VLN-NP inhibited abnormal neovascularization in\n              <jats:italic>Vldlr<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              , oxygen-induced retinopathy, and alkali burn\u2013induced corneal neovascularization models, compared with low-density lipoprotein receptor extracellular domain nanoparticle. VLN-NP significantly inhibited the phosphorylation of low-density lipoprotein receptor-related protein 6, the accumulation of \u03b2-catenin, and the expression of vascular endothelial growth factor in vivo and in vitro.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Taken together, these results suggest that the soluble VLN is a negative regulator of the Wnt pathway and has antiangiogenic activities. Nanoparticle-mediated expression of VLN may thus represent a novel therapeutic approach to treat pathological ocular angiogenesis and potentially other vascular diseases affected by Wnt signaling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.304627","type":"journal-article","created":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T05:28:49Z","timestamp":1423200529000},"page":"855-864","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Nanoparticle-Mediated Expression of a Wnt Pathway Inhibitor Ameliorates Ocular Neovascularization"],"prefix":"10.1161","volume":"35","author":[{"given":"Zhongxiao","family":"Wang","sequence":"first","affiliation":[{"name":"From the Department of Ophthalmology, Shanghai First People\u2019s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Cheng","sequence":"additional","affiliation":[{"name":"From the Department of Ophthalmology, Shanghai First People\u2019s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China (Z.W., X.X.); Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City (Z.W., R.C., K.L., L.D., J.-x.M.); Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora (P.T., U.B.K.); Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China 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