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

Atherosclerosis
Jonathan GolledgePaul E Norman

Abstract

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. 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 (1 microg/kg/min) infusion via subcutaneous pumps until death or 17 weeks when the aortas were harvested and maximum aortic diameters were recorded. Suprarenal aortic segments were assessed for OPN concentration and macrophage accumulation. Saline infused mice served as negative controls (n=22). 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+/-0.11 mm, p=0.011) and fenofibrate (mean diameter 1.51+/-0.13 mm, p=0.001) compared to the vehicle control group (mean diameter 2.10+/-0.14 mm). Immunostaining fo...Continue Reading

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Citations

Jul 27, 2012·Current Atherosclerosis Reports·Hong LuAlan Daugherty
Oct 1, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Sachiko MatsumotoToshiyuki Miyata
May 21, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Jonathan Golledge, Paul E Norman
Sep 3, 2010·Cardiovascular Drugs and Therapy·Jonathan GolledgeCatherine Rush
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Jan 23, 2014·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·P De RangoM Lenti
May 21, 2011·Atherosclerosis·Jonathan Golledge, Paul E Norman
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Oct 21, 2016·Journal of Vascular Surgery·Hisato TakagiUNKNOWN ALICE (All-Literature Investigation of Cardiovascular Evidence) Group
Jun 27, 2017·The British Journal of Surgery·J GolledgeP E Norman
Feb 5, 2016·Vascular Medicine·Hisato TakagiUNKNOWN ALICE (All-Literature Investigation of Cardiovascular Evidence) Group
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