Inhibition of angiogenesis in lipodermatosclerosis: implication for venous ulcer formation.

Abstract

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.

• Authors: Yared Herouy, Sebastian Kreis, Tobias Mueller, Thorsten Duerk, Georg Martiny-Baron, Petra Reusch, Florian May, Marco Idzko, Yohannes Norgauer
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 24 Issue 5 Pg. 645-51 (Nov 2009) ISSN: 1791-244X [Electronic] Greece
• PMID: 19787198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-1
• Angiopoietin-2
• Vascular Endothelial Growth Factor A
• Receptor, TIE-2
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Angiopoietin-1 (genetics, metabolism)
• Angiopoietin-2 (genetics, metabolism)
• Gene Expression Regulation
• Humans
• Immunoblotting
• Neovascularization, Pathologic (complications)
• Receptor, TIE-2 (genetics, metabolism)
• Sclerosis (blood, complications, genetics, pathology)
• Varicose Ulcer (complications, pathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (genetics, metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (genetics, metabolism)