Sildenafil induces angiogenic response in human coronary arteriolar endothelial cells through the expression of thioredoxin, hemeoxygenase and vascular endothelial growth factor
- 作者：Ramesh Vidavalur ; Suresh Varma Penumathsa ; Lijun Zhan ; Mahesh Thirunavukkarasu and Nilanjana Maulik
- 关键词：Angiogenesis ; Hemeoxygenase ; Thioredoxin ; VEGF ; Angiopoietin-1 ; Tuborogenesis
- 刊名：Vascular Pharmacology
- 出版年：2006
- 期刊代码：59_15371891
- 类别：pha
- 出版时间：August 2006
- 卷：45
- 期：2
- 页码：91-95
- 文件大小：264 K
摘要
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 μM) 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 μM 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.