Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm

Golledge Jonathan, Cullen, Bradford, Rush, Catherine, Moran Corey S., Secomb, Emma, Wood, Frances, Daugherty, Alan, Campbell, Julie H. and Norman, Paul E. (2010) Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm. Atherosclerosis, 210 1: 51-56. doi:10.1016/j.atherosclerosis.2009.10.027

Author Golledge Jonathan
Cullen, Bradford
Rush, Catherine
Moran Corey S.
Secomb, Emma
Wood, Frances
Daugherty, Alan
Campbell, Julie H.
Norman, Paul E.
Title Peroxisome proliferator-activated receptor ligands reduce aortic dilatation in a mouse model of aortic aneurysm
Journal name Atherosclerosis   Check publisher's open access policy
ISSN 0021-9150
Publication date 2010-05-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.atherosclerosis.2009.10.027
Volume 210
Issue 1
Start page 51
End page 56
Total pages 6
Editor Steve Humphries
Place of publication Shannon, Ireland
Publisher Elsevier Ireland
Language eng
Subject C1
Formatted abstract
Objective: Osteopontin (OPN) is associated with human abdominal aortic aneurysms (AAA) and in vitro
studies suggest that this cytokine is downregulated by peroxisome proliferator-activated receptor (PPAR)
ligation. We examined the effect of two PPAR ligands within a mouse model of aortic aneurysm.
Methods: At 11 weeks of age apolipoprotein E deficient (ApoE−/−) mice were given pioglitazone (n = 27),
fenofibrate (n = 27) or vehicle (n = 27) in their drinking water. From 13 weeks of age mice received
angiotensin II (1µg/kg/min) infusion via subcutaneous pumps until death or 17 weeks when the aortas
were harvested andmaximumaortic diameters were recorded. Suprarenal aortic segments were assessed
for OPN concentration and macrophage accumulation. Saline infused mice served as negative controls
(n = 22).
Results: Angiotensin II induced marked dilatation in the suprarenal aorta (>2-fold increase compared
to controls) associated with upregulation of the cytokines OPN and macrophage infiltration.
Suprarenal aortic expansion was significantly reduced by administration of pioglitazone (mean diameter
1.61±0.11mm, p = 0.011) and fenofibrate (mean diameter 1.51±0.13mm, p = 0.001) compared to the
vehicle control group (mean diameter 2.10±0.14 mm). Immunostaining for macrophages was reduced
in mice treated with pioglitazone (median staining area 6.2%, interquartile range 4.1–7.2, p < 0.001) and
fenofibrate (median staining area 4.0%, interquartile range 2.2–6.1, p < 0.001) compared to mice receiving
vehicle control (median staining area 13.2%, interquartile range 8.4–20.0).
Conclusion: These findings suggest the potential value of peroxisome proliferator-activated receptor
ligation as a therapy for human AAAs.
© 2009 Elsevier Ireland Ltd. All rights reserved.
Keyword Aortic aneurysm
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 29 October 2009

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Created: Fri, 30 Apr 2010, 01:33:12 EST by Julie Osborne on behalf of Aust Institute for Bioengineering & Nanotechnology