caa a22 4500 445354933 CHVBK 20180317142856.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10238-010-0109-2 doi (NATIONALLICENCE)springer-10.1007/s10238-010-0109-2 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 [Elektronische Daten] [Yuji Ishibashi, Takanori Matsui, Masayoshi Takeuchi, Sho-ichi Yamagishi] 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 30nM vardenafil or 5μM 8-Br-cGMP, 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 AGE-induced 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. Springer-Verlag, 2010 AGE nationallicence Atherosclerosis nationallicence cGMP nationallicence RAGE nationallicence Vardenafil nationallicence Ishibashi Yuji Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut Matsui Takanori Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut Takeuchi Masayoshi Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan aut Yamagishi Sho-ichi Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut Clinical and Experimental Medicine Springer Milan 11/2(2011-06-01), 131-135 1591-8890 11:2<131 2011 11 10238 https://doi.org/10.1007/s10238-010-0109-2 text/html Onlinezugriff via DOI 1 brief-communication jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10238-010-0109-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ishibashi Yuji Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut NATIONALLICENCE 700 1- Matsui Takanori Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut NATIONALLICENCE 700 1- Takeuchi Masayoshi Department of Pathophysiological Science, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan aut NATIONALLICENCE 700 1- Yamagishi Sho-ichi Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan aut NATIONALLICENCE 773 0- Clinical and Experimental Medicine Springer Milan 11/2(2011-06-01), 131-135 1591-8890 11:2<131 2011 11 10238 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer