Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end product (AGE)-induced up-regulation of monocyte chemoattractant protein-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression via elevation of cGMP
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Yuji Ishibashi Takanori Matsui Masayoshi Takeuchi Sho-ichi Yamagishi
- چاپ و سال / کشور: 2010
Description
Decreased production and/or impaired action of nitric oxide (NO) play a role in the pathogenesis of atherosclerotic cardiovascular disease and erectile dysfunction (ED) in diabetic patients. Under hyperglycemic conditions, formation and accumulation of advanced glycation end products (AGE) have been known to progress, thus contributing to tissue damage in diabetes. However, effects of inhibitors of phosphodiesterase-5 (PDE-5), an enzyme that catalyzes the degradation of cyclic guanosin-monophosphate (cGMP) and subsequently blocks the actions of NO, on AGE-exposed endothelial cells remain unknown. Therefore, this study investigated whether and how vardenafil, an inhibitor of PDE-5, could block the deleterious effects of AGE on human umbilical vein endothelial cells (HUVEC). Gene and protein expression was analyzed in quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) and western blots, respectively. Intracellular formation of reactive oxygen species (ROS) was evaluated with dihydroethidium staining. AGE increased receptor for AGE (RAGE) mRNA and protein levels in HUVEC, both of which were significantly inhibited by the treatments with 30 nM vardenafil or 5 lM 8-BrcGMP, an analogue of cGMP. Further, vardenafil reduced the AGE-induced ROS generation and subsequently inhibited up-regulation of monocyte chemoattractant protein-1 (MCP-1) mRNA levels in HUVEC. We demonstrated here for the first time that vardenafil could block the AGEinduced up-regulation of MCP-1 mRNA levels in HUVEC by suppressing RAGE expression and subsequent ROS generation via elevation of cGMP. Our present results suggest that vardenafil directly acts on endothelial cells and it could work as an anti-inflammatory agent against AGE
Clin Exp Med (2011) 11:131–135 DOI 10.1007/s10238-010-0109-2 Received: 15 June 2010 / Accepted: 5 August 2010 / Published online: 29 August 2010
