PMID- 15023892
OWN - NLM
STAT- MEDLINE
DCOM- 20040715
LR  - 20220331
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 109
IP  - 12
DP  - 2004 Mar 30
TI  - Irbesartan but not amlodipine suppresses diabetes-associated atherosclerosis.
PG  - 1536-42
AB  - BACKGROUND: It remains controversial whether specific blockade of the 
      renin-angiotensin system confers superior antiatherosclerotic effects over other 
      antihypertensive agents in diabetes. Therefore, the aim of this study was to 
      compare equihypotensive doses of the angiotensin II subtype 1 (AT1) receptor 
      blocker irbesartan with the calcium antagonist amlodipine on diabetes-induced 
      plaque formation in the apolipoprotein E (apoE)-null mouse and to explore 
      molecular and cellular mechanisms linked to vascular protection. METHODS AND 
      RESULTS: Diabetes was induced by injection of streptozotocin in 6-week-old 
      apoE-null mice. Diabetic animals were randomized to no treatment, irbesartan, or 
      amlodipine for 20 weeks. Diabetes was associated with an increase in plaque area 
      and complexity in the aorta in association with a significant increase in aortic 
      AT1 receptor expression, cellular proliferation, collagen content, macrophage- 
      and alpha-smooth muscle actin-positive cell infiltration, as well as an increased 
      expression of platelet-derived growth factor-B (PDGF-B), monocyte chemoattractant 
      protein-1 (MCP-1), and vascular cell adhesion molecule-1 (VCAM-1). Irbesartan but 
      not amlodipine treatment attenuated the development of atherosclerosis, collagen 
      content, cellular proliferation, and macrophage infiltration as well as 
      diabetes-induced AT1 receptor, PDGF-B, MCP-1, and VCAM-1 overexpression in the 
      aorta despite similar blood pressure reductions by both treatments. CONCLUSIONS: 
      Diabetes-associated atherosclerosis is ameliorated by AT1 receptor blockade but 
      not by calcium channel antagonism, providing further evidence for the vascular 
      renin-angiotensin system playing a pivotal role in the development and 
      acceleration of atherosclerosis in diabetes.
FAU - Candido, Riccardo
AU  - Candido R
AD  - Vascular Division, Baker Heart Research Institute, PO Box 6492, Melbourne 8008, 
      Victoria, Australia.
FAU - Allen, Terri J
AU  - Allen TJ
FAU - Lassila, Markus
AU  - Lassila M
FAU - Cao, Zemin
AU  - Cao Z
FAU - Thallas, Vicki
AU  - Thallas V
FAU - Cooper, Mark E
AU  - Cooper ME
FAU - Jandeleit-Dahm, Karin A
AU  - Jandeleit-Dahm KA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040315
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Tetrazoles)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 1J444QC288 (Amlodipine)
RN  - 5W494URQ81 (Streptozocin)
RN  - 9007-34-5 (Collagen)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - Amlodipine/pharmacology/*therapeutic use
MH  - *Angiotensin II Type 1 Receptor Blockers
MH  - Animals
MH  - Antihypertensive Agents/pharmacology/*therapeutic use
MH  - Aortic Diseases/etiology/metabolism/pathology/prevention & control
MH  - Apolipoproteins E/deficiency/genetics
MH  - Arteriosclerosis/etiology/metabolism/pathology/*prevention & control
MH  - Biphenyl Compounds/pharmacology/*therapeutic use
MH  - Calcium Channel Blockers/pharmacology/*therapeutic use
MH  - Cell Division
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Collagen/metabolism
MH  - Diabetes Mellitus, Experimental/*complications
MH  - Drug Evaluation, Preclinical
MH  - Gene Expression Regulation/drug effects
MH  - Irbesartan
MH  - Macrophages/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-sis/biosynthesis/genetics
MH  - Receptor, Angiotensin, Type 1/biosynthesis/genetics/physiology
MH  - Renin-Angiotensin System/drug effects/physiology
MH  - Streptozocin
MH  - Tetrazoles/pharmacology/*therapeutic use
MH  - Vascular Cell Adhesion Molecule-1/biosynthesis/genetics
EDAT- 2004/03/17 05:00
MHDA- 2004/07/16 05:00
CRDT- 2004/03/17 05:00
PHST- 2004/03/17 05:00 [pubmed]
PHST- 2004/07/16 05:00 [medline]
PHST- 2004/03/17 05:00 [entrez]
AID - 01.CIR.0000124061.78478.94 [pii]
AID - 10.1161/01.CIR.0000124061.78478.94 [doi]
PST - ppublish
SO  - Circulation. 2004 Mar 30;109(12):1536-42. doi: 
      10.1161/01.CIR.0000124061.78478.94. Epub 2004 Mar 15.