Three reactive compartments in venous malformations.
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.
Ebenebe
Chinedu U
CU
Children's Hospital, Pediartics I, University of Goettingen, Goettingen, Germany.
Diehl
Stefanie
S
Bartnick
Katja
K
Dörge
Hilmar
H
Becker
Jürgen
J
Schweigerer
Lothar
L
Wilting
Jörg
J
D001483:Base Sequence; D001808:Blood Vessels / Q000002:abnormalities* / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D036342:Ephrins / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012501:Saphenous Vein / Q000002:abnormalities / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics
D018925:Chemokines; D017931:DNA Primers; D036342:Ephrins; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D014157:Transcription Factors