Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor.
This study was undertaken to investigate the effect of phosphodiesterase-5 (PDE5) inhibitor, sildenafil, on angiogenic response in human coronary arteriolar endothelial cells (HCAEC). The cells exposed to sildenafil (1-20 microM) demonstrated significantly accelerated tubular morphogenesis with the induction of thioredoxin-1 (Trx-1), hemeoxygenase-1 (HO-1) and VEGF. Sildenafil induced VEGF and angiopoietin specific receptors such as KDR, Tie-1 and Tie-2. This angiogenic response was repressed by tinprotoporphyrin IX (SnPP), an inhibitor of HO-1 enzyme activity. Sildenafil below 1 muM has no angiogenic effect as evidenced by reduced tuborogenesis. Sildenafil along with SnPP inhibited both VEGF and Angiopoietin-1 (Ang-1) protein expression. Therefore our results demonstrated for the first time that sildenafil is a very potent pro-angiogenic factor.
Vidavalur
Ramesh
R
Department of Pediatrics, University of Connecticut Health Center, Farmington, CT 06030-1110, USA.
Penumathsa
Suresh Varma
SV
Zhan
Lijun
L
Thirunavukkarasu
Mahesh
M
Maulik
Nilanjana
N
D001160:Arterioles / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013879:Thioredoxins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; D013879:Thioredoxins; D000068677:Sildenafil Citrate; D006419:Heme Oxygenase (Decyclizing)