Three reactive compartments in venous malformations

Chinedu U. Ebenebe; Stefanie Diehl; Katja Bartnick; Hilmar Dörge; Jürgen Becker; Lothar Schweigerer; Jörg Wilting

doi:10.1160/TH07-01-0021

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2007; 97(05): 763-773
DOI: 10.1160/TH07-01-0021

Theme Issue Article

Schattauer GmbH

Three reactive compartments in venous malformations

Chinedu U. Ebenebe^*

¹Children’s Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany

,

Stefanie Diehl^*

¹Children’s Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany

²Kinderklinik und Poliklinik, Klinikum der Bayerischen Julius-Maximilians-Universität, Würzburg, Germany

,

Katja Bartnick

¹Children’s Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany

,

Hilmar Dörge

³Department of Thoracic and Cardiovascular Surgery, University of Goettingen, Goettingen, Germany

,

Jürgen Becker

¹Children’s Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany

,

Lothar Schweigerer

⁴Klinik für Kinder- und Jugendmedizin, Helios Klinikum Berlin-Buch, Berlin, Germany

,

Jörg Wilting

¹Children’s Hospital, Pediatrics I, University of Goettingen, Goettingen, Germany

› Institutsangaben

Abstract

Summary

Vascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50% of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown. We have performed a global comparison of gene expression in slow-flow VMs and normal saphenous veins using human whole genome micro-arrays.Genes of interest were validated with qRT-PCR. Gene expression in the tunica media was studied after laser micro-dissection of small pieces of tissue. Protein expression in endothelial cells (ECs) was studied with antibodies.We detected 511 genes more than four-fold down- and 112 genes more than four-fold up-regulated. Notably, chemokines, growth factors, transcription factors and regulators of extra-cellular matrix (ECM) turnover were regulated. We observed activation and “arterialization” of ECs of the VM proper, whereas ECs of vasa vasorum exhibited up-regulation of inflammation markers. In the tunica media, an altered ECM turnover and composition was found. Our studies demonstrate dysregulated gene expression in tunica interna, media and externa of VMs, and show that each of the three layers represents a reactive compartment.The dysregulated genes may serve as therapeutic targets.

Keywords

Venous malformation - chemokines - growth factors - transcription factors - extracellular matrix

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