PMID- 20803229
OWN - NLM
STAT- MEDLINE
DCOM- 20110809
LR  - 20211020
IS  - 1591-9528 (Electronic)
IS  - 1591-8890 (Linking)
VI  - 11
IP  - 2
DP  - 2011 Jun
TI  - 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.
PG  - 131-5
LID - 10.1007/s10238-010-0109-2 [doi]
AB  - 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 muM 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.
FAU - Ishibashi, Yuji
AU  - Ishibashi Y
AD  - Department of Pathophysiology and Therapeutics of Diabetic Vascular 
      Complications, Kurume University School of Medicine, Japan.
FAU - Matsui, Takanori
AU  - Matsui T
FAU - Takeuchi, Masayoshi
AU  - Takeuchi M
FAU - Yamagishi, Sho-ichi
AU  - Yamagishi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100829
PL  - Italy
TA  - Clin Exp Med
JT  - Clinical and experimental medicine
JID - 100973405
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Imidazoles)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Piperazines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Sulfones)
RN  - 0 (Triazines)
RN  - 5O8R96XMH7 (Vardenafil Dihydrochloride)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - Cyclic GMP/*metabolism
MH  - Endothelial Cells/*drug effects
MH  - Gene Expression Profiling
MH  - Glycation End Products, Advanced/*metabolism
MH  - Humans
MH  - Imidazoles/*metabolism
MH  - Phosphodiesterase 5 Inhibitors/*metabolism
MH  - Piperazines/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/*antagonists & inhibitors
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sulfones/metabolism
MH  - Triazines/metabolism
MH  - Up-Regulation
MH  - Vardenafil Dihydrochloride
EDAT- 2010/08/31 06:00
MHDA- 2011/08/10 06:00
CRDT- 2010/08/31 06:00
PHST- 2010/06/15 00:00 [received]
PHST- 2010/08/05 00:00 [accepted]
PHST- 2010/08/31 06:00 [entrez]
PHST- 2010/08/31 06:00 [pubmed]
PHST- 2011/08/10 06:00 [medline]
AID - 10.1007/s10238-010-0109-2 [doi]
PST - ppublish
SO  - Clin Exp Med. 2011 Jun;11(2):131-5. doi: 10.1007/s10238-010-0109-2. Epub 2010 Aug 
      29.