PMID- 16023123
OWN - NLM
STAT- MEDLINE
DCOM- 20060420
LR  - 20071115
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 184
IP  - 2
DP  - 2006 Feb
TI  - Transiently heightened angiotensin II has distinct effects on atherosclerosis and 
      aneurysm formation in hyperlipidemic mice.
PG  - 312-21
AB  - Experimentally sustained increase in angiotensin II (AngII) promotes tissue 
      destruction in various cardiovascular disorders. We examined whether transiently 
      heightened AngII affects subsequent atherosclerosis and aneurysm formation. AngII 
      or saline was administered for 2 weeks to apolipoprotein E (apoE)-deficient mice. 
      Mice were sacrificed at the end of the 2-week infusion or 6- or 14 weeks later. 
      Short-term AngII did not affect atherosclerosis immediately following the 
      infusion or 6 weeks later. By contrast, 14 weeks after infusion there was 
      remarkably more atherosclerosis in previously AngII-exposed mice. Preceding the 
      build up of atherosclerotic lesions, AngII-exposure increased mRNA expression and 
      immunostaining of monocyte chemoattractant protein-1 (MCP-1) and its receptor, 
      CCR2. This was followed by greater macrophage-positivity in AngII-exposed aortae. 
      In contrast to the delayed effects on atherosclerosis, 20% of mice were found to 
      have abdominal aneurysms at the end of AngII-exposure. This effect was not 
      contingent on blood pressure. Moreover, despite amplification in atherosclerosis 
      following AngII, no aneurysms were found 14 weeks later. Our studies reveal that 
      even transient exposure to AngII primes the vessel for subsequent amplification 
      of atherosclerosis which involves activation of MCP-1/CCR2 and influx of 
      macrophages into the nascent atherosclerotic plaque. By contrast, transient 
      AngII-exposure causes prompt aneurysm formation that does not parallel 
      atherosclerosis and disappears even in the face of progressively greater 
      atherosclerotic lesions.
FAU - Ayabe, Nobuhiko
AU  - Ayabe N
AD  - Department of Pediatrics, MCN C4204, Vanderbilt University Medical Center, 
      Nashville, TN 37232-2584, USA.
FAU - Babaev, Vladimir R
AU  - Babaev VR
FAU - Tang, Yiwei
AU  - Tang Y
FAU - Tanizawa, Takakuni
AU  - Tanizawa T
FAU - Fogo, Agnes B
AU  - Fogo AB
FAU - Linton, Macrae F
AU  - Linton MF
FAU - Ichikawa, Iekuni
AU  - Ichikawa I
FAU - Fazio, Sergio
AU  - Fazio S
FAU - Kon, Valentina
AU  - Kon V
LA  - eng
GR  - DK37868/DK/NIDDK NIH HHS/United States
GR  - DK44757/DK/NIDDK NIH HHS/United States
GR  - DK59637-01/DK/NIDDK NIH HHS/United States
GR  - HL53989/HL/NHLBI NIH HHS/United States
GR  - HL57986/HL/NHLBI NIH HHS/United States
GR  - HL65709/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20050714
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 11128-99-7 (Angiotensin II)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Angiotensin II/administration & dosage/metabolism/*toxicity
MH  - Animals
MH  - Aorta, Thoracic/drug effects/pathology
MH  - Aortic Aneurysm, Thoracic/*etiology/metabolism/pathology
MH  - Apolipoproteins E/deficiency
MH  - Atherosclerosis/*etiology/metabolism/pathology
MH  - Chemokine CCL2/drug effects/genetics/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Follow-Up Studies
MH  - Hyperlipidemias/*complications/metabolism
MH  - Immunohistochemistry
MH  - Infusions, Intravenous
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA/genetics
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/drug effects/genetics/metabolism
EDAT- 2005/07/19 09:00
MHDA- 2006/04/21 09:00
CRDT- 2005/07/19 09:00
PHST- 2005/02/24 00:00 [received]
PHST- 2005/04/22 00:00 [revised]
PHST- 2005/05/04 00:00 [accepted]
PHST- 2005/07/19 09:00 [pubmed]
PHST- 2006/04/21 09:00 [medline]
PHST- 2005/07/19 09:00 [entrez]
AID - S0021-9150(05)00312-6 [pii]
AID - 10.1016/j.atherosclerosis.2005.05.016 [doi]
PST - ppublish
SO  - Atherosclerosis. 2006 Feb;184(2):312-21. doi: 
      10.1016/j.atherosclerosis.2005.05.016. Epub 2005 Jul 14.