Lipodermatosclerosis refers to skin induration of the lower extremities characterized by tortuous, hyperpermeable vessels preceding venous leg ulcerations.
Protein ligands and
receptor tyrosine kinases that specifically regulate endothelial cell function are mainly involved in physiological as well as in disease-related angiogenesis. These
ligand/receptor systems include the
vascular endothelial growth factor (
VEGF) and the
angiopoietin (Ang) families and their receptor the
tyrosine kinase with immunoglobulin-like domains (Tie-2) as well as the
VEGF receptor family (VEGF-R1 and VEGF-R2). In the present study, the contribution of these endothelium-specific
ligand/receptor systems in tissue samples of
lipodermatosclerosis was evaluated. Our results provide evidence, that the
mRNA-transcripts of
VEGF (p<0.01), Ang-1 (p<0.1), Ang-2 (p<0.1) and VEGF-R1 (p<0.01) were significantly upregulated in all samples of
lipodermatosclerosis in comparison with healthy skin by using
reverse transcriptase-polymerase chain reaction. On
protein level
VEGF (p<0.01), Ang-1 (p<0.1), Ang-2 (p<0.1) and VEGF-R1 (p<0.01) were significantly elevated as well. Solely for Tie-2 and for VEGF-R2 no statistical difference could be detected on
mRNA and
protein level in patients with
lipodermatosclerosis in comparison with healthy skin. By immunohistochemistry we confirmed upregulated
protein expression for
VEGF, Ang-1, Ang-2 and VEGF-R1 compared with healthy skin. Our findings strongly suggest that an imbalance between these
ligand/receptor systems might contribute to the pathophysiology of advanced stages of chronic
venous insufficiency. Inhibition of angiogenesis could significantly impact the tissue breakdown in
lipodermatosclerosis and could hereby enable the formation of venous leg ulcerations.