title: Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations.
abstract: Despite multiple previous studies in the field of vascular anomalies, the mechanism(s) leading to their development, progression and maintenance has remained unclear. In this study, we have characterized the expression levels of vascular endothelial growth factors and their receptors in 33 human vascular anomalies. Analysis with quantitative real-time PCR and gene-specific assays showed higher expression of neuropilin-2 (NRP2) and VEGF-receptor-3 (VEGFR-3) mRNAs in vascular malformations (VascM) as compared to infantile hemangiomas (Hem). In addition, the expression levels of PlGF and VEGF-C mRNA were significantly higher in venous VascM when compared to the other VascM and Hem. Higher expression of NRP2 and VEGFR-3 were confirmed by immunohistochemistry. To further study the importance of NRP2 and VEGFR-3, endothelial cell (EC) cultures were established from vascular anomalies. It was found that NRP2 and VEGFR-3 mRNA levels were significantly higher in some of the VascM ECs as compared to human umbilical vein ECs which were used as control cells in the study. Furthermore, adenoviral delivery of soluble decoy NRP2 prevented the proliferation of ECs isolated from most of the vascular anomalies. Our findings suggest that NRP2 functions as a factor maintaining the pathological vascular network in these anomalies. Thus, NRP2 could become a potential therapeutic target for the diagnosis and treatment of vascular anomalies.
authors.affiliation: Department of Surgery, South Karelia Central Hospital, Lappeenranta, Finland.
authors.forename: Taina A
authors.initials: TA
authors.lastname: Partanen
authors.forename: Pia
authors.initials: P
authors.lastname: Vuola
authors.forename: Suvi
authors.initials: S
authors.lastname: Jauhiainen
authors.forename: Jouko
authors.initials: J
authors.lastname: Lohi
authors.forename: Päivi
authors.initials: P
authors.lastname: Salminen
authors.forename: Anne
authors.initials: A
authors.lastname: Pitkäranta
authors.forename: Sanna-Kaisa
authors.initials: SK
authors.lastname: Häkkinen
authors.forename: Krista
authors.initials: K
authors.lastname: Honkonen
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003710:Demography; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D018324:Hemangioma, Capillary / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000378:metabolism / Q000473:pathology; D039943:Neuropilin-2 / Q000235:genetics* / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics* / Q000378:metabolism; D054079:Vascular Malformations / Q000235:genetics* / Q000473:pathology*
chemical_list: D039943:Neuropilin-2; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C581308:neuropilin-2, human; D000072483:Placenta Growth Factor; C581309:FLT4 protein, human; D040321:Vascular Endothelial Growth Factor Receptor-3