No abstract

SummaryVascular malformations affect3 %o fn eonates.V enous malformations(VMs)are the largest group representing morethan 50% of cases. In hereditary forms of VMs gene mutations have been identified,but forthe large groupofspontaneous forms the primaryc ause and downstreamd ysregulated genesa re unknown. We have performedag lobal comparison of gene expression in slow-flow VMs and normal saphenous veins using human whole genomemicro-arrays.Genes of interest were validated with qRT-PCR.Genee xpression in the tunica media was studied after laser micro-dissection of smallp ieceso ft issue. Proteine xpression in endothelialc ells (ECs) was studied with antibodies.Wed etected5 11 genesm oret han four-foldd ownKeywords Ve nous malformation,chemokines,growth factors,transcription factors, extracellular matrix and 112g enes moret han four-foldu p-regulated. Notably, chemokines,growth factors,transcriptionfactors and regulators of extra-cellular matrix (ECM) turnoverw erer egulated. We observed activation and "arterialization" of ECs of theVM proper, whereas ECsof vasa vasorum exhibited up-regulationofinflammation markers. In the tunicam edia,ana ltered ECM turnover and composition was found.Our studies demonstratedysregulated gene expression in tunica interna, media and externa of VMs, and showt hat each of the three layers represents ar eactive compartment.Thedysregulated genesmay serveastherapeutic targets.