PMID- 21575596
OWN - NLM
STAT- MEDLINE
DCOM- 20110808
LR  - 20211203
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 409
IP  - 2
DP  - 2011 Jun 3
TI  - Irbesartan attenuates ischemic brain damage by inhibition of MCP-1/CCR2 signaling 
      pathway beyond AT(1) receptor blockade.
PG  - 275-9
LID - 10.1016/j.bbrc.2011.04.142 [doi]
AB  - Angiotensin II type 1 (AT(1)) receptor blockers (ARBs) are known to prevent the 
      onset of stroke and to attenuate neural damage. Additional beneficial effects of 
      ARBs, independent of AT(1) receptor blockade, have been highlighted. Irbesartan 
      is reported to act as an antagonist of the monocyte chemoattractant protein-1 
      (MCP-1) receptor, C-C chemokine receptor 2 (CCR2), due to its molecular 
      structure. We examined the possible synergistic effects of co-administration of 
      irbesartan with propagermanium, a CCR2 antagonist, on ischemic brain damage. 
      Administration of propagermanium decreased ischemic brain area after middle 
      cerebral artery occlusion (MCAO). To study the possible synergistic effects of 
      propagermanium with ARBs, we employed non-effective lower doses of irbesartan and 
      losartan. Administration of irbesartan with propagermanium decreased the ischemic 
      brain area more markedly compared with propagermanium alone, but 
      co-administration of losartan did not. MCP-1 mRNA level was significantly 
      increased on the ipsilateral side after MCAO, and administration of irbesartan 
      with propagermanium decreased the MCP-1 level, whereas co-administration of 
      losartan did not. Similar results were obtained for MCP-1 protein level. CCR2 
      mRNA expression was significantly elevated on the ipsilateral side; however, no 
      significant difference was observed between each group. mRNA levels of other 
      inflammatory cytokines such as TNF-alpha and IL-1beta also significantly increased on 
      the ipsilateral side, but the expression levels were not changed by each drug 
      treatment. Taking these findings together, irbesartan exerts more beneficial 
      effects on ischemic brain damage with an MCP-1 receptor blocker, at least due to 
      its inhibitory effects on MCP-1/CCR2 signaling beyond AT(1) receptor blockade.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Tsukuda, Kana
AU  - Tsukuda K
AD  - Department of Molecular Cardiovascular Biology and Pharmacology, Ehime 
      University, Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295, 
      Japan.
FAU - Mogi, Masaki
AU  - Mogi M
FAU - Iwanami, Jun
AU  - Iwanami J
FAU - Min, Li-Juan
AU  - Min LJ
FAU - Jing, Fei
AU  - Jing F
FAU - Oshima, Kousei
AU  - Oshima K
FAU - Horiuchi, Masatsugu
AU  - Horiuchi M
LA  - eng
PT  - Journal Article
DEP - 20110514
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Organometallic Compounds)
RN  - 0 (Propionates)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Tetrazoles)
RN  - 00072J7XWS (Germanium)
RN  - 1Q2P9TO9Q7 (propagermanium)
RN  - J0E2756Z7N (Irbesartan)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*therapeutic use
MH  - Animals
MH  - Biphenyl Compounds/*therapeutic use
MH  - Brain Ischemia/*drug therapy/pathology
MH  - Germanium
MH  - Irbesartan
MH  - Losartan/therapeutic use
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Organometallic Compounds/therapeutic use
MH  - Propionates
MH  - Receptors, CCR2/*antagonists & inhibitors/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Tetrazoles/*therapeutic use
EDAT- 2011/05/18 06:00
MHDA- 2011/08/09 06:00
CRDT- 2011/05/18 06:00
PHST- 2011/04/28 00:00 [received]
PHST- 2011/04/29 00:00 [accepted]
PHST- 2011/05/18 06:00 [entrez]
PHST- 2011/05/18 06:00 [pubmed]
PHST- 2011/08/09 06:00 [medline]
AID - S0006-291X(11)00751-0 [pii]
AID - 10.1016/j.bbrc.2011.04.142 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2011 Jun 3;409(2):275-9. doi: 
      10.1016/j.bbrc.2011.04.142. Epub 2011 May 14.