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