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Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations

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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.

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Acknowledgments

This study was supported by Finnish Academy, Antti and Tyyne Soininen Foundation and Kuopio University Foundation. We thank Seija Sahrio for technical assistance in immunohistochemistry, Sari Järveläinen and Tiina Koponen for preparing adenoviral vectors, and Dr. Johanna Lähteenvuo for invaluable advises in endothelial cell isolation.

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Authors and Affiliations

  1. Department of Surgery, South Karelia Central Hospital, Lappeenranta, Finland

    Taina A. Partanen

  2. Division of Plastic Surgery, Department of Surgery, Helsinki University Hospital, Helsinki, Finland

    Pia Vuola

  3. Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio Campus, Neulaniementie 2, PO Box 1627, 70211, Kuopio, Finland

    Suvi Jauhiainen, Sanna-Kaisa Häkkinen, Krista Honkonen & Seppo Ylä-Herttuala

  4. Department of Pathology, Helsinki University Hospital, Helsinki, Finland

    Jouko Lohi

  5. Department of Pediatric Surgery, Helsinki University Hospital, Helsinki, Finland

    Päivi Salminen

  6. Department Otorhinolaryngology, Helsinki University Hospital, Helsinki, Finland

    Anne Pitkäranta

  7. Molecular/Cancer Biology Program, Institute for Molecular Medicine Finland, Haartman Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland

    Kari Alitalo

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  1. Taina A. Partanen
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Corresponding author

Correspondence to Seppo Ylä-Herttuala.

Additional information

Taina A. Partanen, Pia Vuola and Suvi Jauhiainen contributed equally to the work.

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Partanen, T.A., Vuola, P., Jauhiainen, S. et al. Neuropilin-2 and vascular endothelial growth factor receptor-3 are up-regulated in human vascular malformations. Angiogenesis 16, 137–146 (2013). https://doi.org/10.1007/s10456-012-9305-x

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  • DOI: https://doi.org/10.1007/s10456-012-9305-x

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