PMID- 20379053
OWN - NLM
STAT- MEDLINE
DCOM- 20101028
LR  - 20190608
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Linking)
VI  - 17
IP  - 6
DP  - 2010 Jun 30
TI  - Blockade of renin-angiotensin system attenuates advanced glycation end 
      products-mediated signaling pathways.
PG  - 590-600
AB  - AIM: Advanced glycation end products (AGE) and a receptor for AGE (RAGE) play a 
      key role in diabetic vascular complications. Matrix metalloproteinases (MMPs) and 
      apoptosis contribute to plaque instability. The renin-angiotensin system (RAS) is 
      crucial for NADPH oxidase-dependent redox signaling pathways in the vascular 
      wall. We investigated the effects of RAS blockade on AGE-triggered signaling 
      pathways and its downstream events, including MMP-9 and apoptosis. METHODS: We 
      used cultured rabbit aortic smooth muscle cells (SMCs), which were stimulated 
      with AGE in the presence or absence of temocaprilat or olmesartan. RESULTS: 
      Angiotensin converting enzyme (ACE) mRNA levels were increased 4 to 6 hours after 
      adding AGE. AGE induced Rac1 and p47(phox) membrane translocation, reactive 
      oxygen species (ROS) generation and NF-kappaB phosphorylation within 15 minutes, 
      and various molecular expressions after 18 hours, which were attenuated by RAS 
      blockade by temocaprilat or olmesartan. AGE-induced RAGE expression, as well as 
      other molecules, including membrane type 1-MMP (MT1-MMP), monocyte 
      chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1), 
      was NADPH oxidase signaling-dependent and blunted by temocaprilat and olmesartan. 
      The parameters of plaque instability, including MMP-9 expression and activity, 
      and apoptosis were up-regulated by AGE, which was markedly attenuated by 
      temocaprilat or olmesartan. Using isolated human monocyte culture, AGE-induced 
      ROS generation and molecular expression were also attenuated by RAS blockade. 
      CONCLUSION: The present study shows that AGE-triggered NADPH oxidase signaling 
      pathways, including MMP-9 and apoptosis, were attenuated by RAS blockade, which 
      may be an attractive strategy for treating plaque instability in diabetic 
      vascular complications.
FAU - Kamioka, Masashi
AU  - Kamioka M
AD  - Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, 
      Japan.
FAU - Ishibashi, Toshiyuki
AU  - Ishibashi T
FAU - Sugimoto, Koichi
AU  - Sugimoto K
FAU - Uekita, Hironori
AU  - Uekita H
FAU - Nagai, Ryoji
AU  - Nagai R
FAU - Sakamoto, Nobuo
AU  - Sakamoto N
FAU - Ando, Katsuya
AU  - Ando K
FAU - Ohkawara, Hiroshi
AU  - Ohkawara H
FAU - Teramoto, Tamio
AU  - Teramoto T
FAU - Maruyama, Yukio
AU  - Maruyama Y
FAU - Takeishi, Yasuchika
AU  - Takeishi Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100402
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Imidazoles)
RN  - 0 (Tetrazoles)
RN  - 0 (Thiazepines)
RN  - 2D6A12Q12R (temocaprilat)
RN  - 8W1IQP3U10 (olmesartan)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Animals
MH  - Aorta/cytology
MH  - Cells, Cultured
MH  - Diabetic Angiopathies/drug therapy
MH  - Glycation End Products, Advanced/*pharmacology
MH  - Imidazoles/pharmacology
MH  - Myocytes, Smooth Muscle
MH  - NADPH Oxidases/metabolism
MH  - Rabbits
MH  - Renin-Angiotensin System/*drug effects
MH  - Signal Transduction/*drug effects
MH  - Tetrazoles/pharmacology
MH  - Thiazepines/pharmacology
EDAT- 2010/04/10 06:00
MHDA- 2010/10/29 06:00
CRDT- 2010/04/10 06:00
PHST- 2010/04/10 06:00 [entrez]
PHST- 2010/04/10 06:00 [pubmed]
PHST- 2010/10/29 06:00 [medline]
AID - JST.JSTAGE/jat/3624 [pii]
AID - 10.5551/jat.3624 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2010 Jun 30;17(6):590-600. doi: 10.5551/jat.3624. Epub 2010 
      Apr 2.