Aminaphtone, a naphtohydrochinone used in the treatment of capillary disorders, may affect oedema in chronic venous insufficiency. Aim of study is to investigate the effect of aminaphtone on vascular endothelial permeability in vitro and its effects on three-dimensional capillary-like structures formed by human umbilical vein endothelial cells.
Method
Human umbilical vein endothelial cells were treated with 50 ng/ml VEGF for 2 h and aminaphtone for 6 h. Permeability assay, VE-cadherin expression and Matrigel assay were performed.
Results
VEGF-induced permeability was significantly decreased by aminaphtone in a range concentration of 1–20 µg/ml. Aminaphtone restored VE-cadherin expression. Finally, 6 h pre-treatment with aminaphtone significantly preserved capillary-like structures formed by human umbilical vein endothelial cells on Matrigel up to 48 h compared to untreated cells.
Conclusions
Aminaphtone significantly protects endothelium permeability and stabilises endothelial cells organised in capillary-like structures, modulating VE-cadherin expression. These data might explain the clinical benefit of aminaphtone on chronic venous insufficiency.
BachTLBarsigianCChalupowiczDGet al.VE-Cadherin mediates endothelial cell capillary tube formation in fibrin and collagen gels. Exp Cell Res1998; 238: 324–334.
8.
BachTLBarsigianCYaenCHet al.Endothelial cell VE-cadherin functions as a receptor for the beta15-42 sequence of fibrin. J Biol Chem1998; 273: 30719–30728.
De AnnaDMariFIntiniSet al.[Effects of therapy with aminaftone on chronic venous and lymphatic stasis]. Minerva Cardioangiol1989; 37: 251–254.
12.
Pereira de GodoyJM. Aminaphtone in idiopathic cyclic oedema syndrome. Phlebology2008; 23: 118–119.
13.
BelczakSQSincosIRCamposWet al.Veno-active drugs for chronic venous disease: a randomized, double-blind, placebo-controlled parallel-design trial. Phlebology2014; 29: 454–460.
14.
ChowdhuryZABarsigianCChalupowiczGDet al.Colocalization of tissue transglutaminase and stress fibers in human vascular smooth muscle cells and human umbilical vein endothelial cells. Exp Cell Res1997; 231: 38–49.
15.
NicolaidesAN. Investigation of chronic venous insufficiency: a consensus statement (France, March 5-9, 1997). Circulation2000; 102: E126–E163.
GulatiOP. Pycnogenol(R) in chronic venous insufficiency and related venous disorders. Phytother Res2014; 28: 348–362.
18.
RameletAA. Pharmacologic aspects of a phlebotropic drug in CVI-associated edema. Angiology2000; 51: 19–23.
19.
ScorzaRSantanielloASalazarGet al.Effects of aminaftone 75 mg TID on soluble adhesion molecules: a 12-week, randomized, open-label pilot study in patients with systemic sclerosis. Clin Ther2008; 30: 924–929.
20.
ScorzaRSantanielloASalazarGet al.Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 cells: an in vitro Study. Drugs R D2008; 9: 251–257.
21.
LevinER. Endothelins. N Engl J Med1995; 333: 356–363.
22.
VanhouttePM. Endothelin-1. A matter of life and breath. Nature1994; 368: 693–694.
LeeKJKimMKParkYHet al.Vascular endothelial growth factor induces endothelin-1 production via matrix metalloproteinase-2 rather than endothelin-converting enzyme-1. Hypertens Preg2007; 26: 189–199.
25.
ChenSApostolovaMDCherianMGet al.Interaction of endothelin-1 with vasoactive factors in mediating glucose-induced increased permeability in endothelial cells. Lab Invest2000; 80: 1311–1321.
26.
FrulliniADa PozzoEFeliceFet al.Prevention of excessive endothelin-1 release in sclerotherapy: in vitro and in vivo studies. Dermatol Surg2014; 40: 769–775.
27.
GumbinerBM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol2005; 6: 622–634.
28.
GavardJGutkindJS. VEGF controls endothelial-cell permeability by promoting the beta-arrestin-dependent endocytosis of VE-cadherin. Nat Cell Biol2006; 8: 1223–1234.
29.
Yamaoka-TojoMTojoTKimHWet al.IQGAP1 mediates VE-cadherin-based cell-cell contacts and VEGF signaling at adherence junctions linked to angiogenesis. Arterioscler Thromb Vasc Biol2006; 26: 1991–1997.
