PMID- 14716205
OWN - NLM
STAT- MEDLINE
DCOM- 20040817
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 43
IP  - 2
DP  - 2004 Feb
TI  - Lesion progression in apoE-deficient mice: implication of chemokines and effect 
      of the AT1 angiotensin II receptor antagonist irbesartan.
PG  - 191-9
AB  - We recently described that a treatment with the angiotensin AT1 receptor 
      antagonist irbesartan inhibits atherosclerotic lesion development, macrophage 
      accumulation, and monocyte chemoattractant protein-1 (MCP-1) as well as the 
      chemokine KC expression in apolipoprotein E-deficient (apoE-deficient) mice. The 
      present study addresses whether these and other chemokines are expressed not only 
      during the initiation but also during the development of atherosclerotic lesions 
      and whether irbesartan can inhibit the expression of these chemokines during 
      lesion progression. The time course of lesion development was assessed in 
      apoE-deficient mice aged 1 to 9 months and the relative expression of chemokines 
      was quantified by RT-PCR. Significant lesion formation already appeared in 
      3-month-old apoE-deficient mice, and progressed further to the age of 9 months. 
      The expression of MCP-1 and KC (the mouse homologue of Groalpha), was induced at 
      1 month in apoE-deficient as compared with wild type (C57/Bl6) mice, and was 
      observed before any detectable histologic changes. MCP-1 and KC expression 
      remained high during lesion progression. The expression of macrophage 
      inflammatory protein-2 (MIP-2, the mouse Grobeta/gamma homologue) and macrophage 
      inflammatory protein-1alpha (MIP-1alpha) was increased in lesions from 
      4-month-old mice onward, whereas Regulated upon Activation of Normal T-cells 
      Expressed and Secreted (RANTES) was significantly induced in 6- to 9-month-old 
      mice only. Irbesartan (50 mg/kg/d) administered from the age of 3 months onward 
      significantly reduced the progression of the lesions as well as the expression of 
      the chemokines. A short-term treatment with irbesartan significantly inhibited 
      the expression of MCP-1 and KC, suggesting that activation of the 
      renin-angiotensin system is involved in up-regulation of these chemokines and 
      that this effect represents a potential mechanism by which irbesartan inhibits 
      plaque development and progression.
FAU - Martin, Genevieve
AU  - Martin G
AD  - Genfit SA, Loos, France.
FAU - Dol, Frederique
AU  - Dol F
FAU - Mares, Anne-Marie
AU  - Mares AM
FAU - Berezowski, Vincent
AU  - Berezowski V
FAU - Staels, Bart
AU  - Staels B
FAU - Hum, Dean W
AU  - Hum DW
FAU - Schaeffer, Paul
AU  - Schaeffer P
FAU - Herbert, Jean-Marc
AU  - Herbert JM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (Tetrazoles)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - *Angiotensin II Type 1 Receptor Blockers
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology/therapeutic use
MH  - Apolipoproteins E/*deficiency
MH  - Arteriosclerosis/*drug therapy/metabolism/pathology
MH  - Biphenyl Compounds/*pharmacology/therapeutic use
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemokine CCL5
MH  - Chemokines/genetics/metabolism
MH  - Female
MH  - Irbesartan
MH  - Mice
MH  - Polymerase Chain Reaction
MH  - Tetrazoles/*pharmacology/therapeutic use
EDAT- 2004/01/13 05:00
MHDA- 2004/08/18 05:00
CRDT- 2004/01/13 05:00
PHST- 2004/01/13 05:00 [pubmed]
PHST- 2004/08/18 05:00 [medline]
PHST- 2004/01/13 05:00 [entrez]
AID - 00005344-200402000-00005 [pii]
AID - 10.1097/00005344-200402000-00005 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2004 Feb;43(2):191-9. doi: 
      10.1097/00005344-200402000-00005.