title: Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Connecticut Health Center, Farmington, CT 06030-1110, USA.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Vidavalur
authors.forename: Suresh Varma
authors.initials: SV
authors.lastname: Penumathsa
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhan
authors.forename: Mahesh
authors.initials: M
authors.lastname: Thirunavukkarasu
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
mesh_terms: 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*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; D013879:Thioredoxins; D000068677:Sildenafil Citrate; D006419:Heme Oxygenase (Decyclizing)