Interaction between Angiotensin II, Osteoprotegrin, and peroxisome proliferator-activated receptor-y in abdominal aortic aneurysm
Moran, Corey S., Cullen, Bradford, Campbell, Julie H., and Golledge, Jonathan (2009) Interaction between Angiotensin II, Osteoprotegrin, and peroxisome proliferator-activated receptor-y in abdominal aortic aneurysm. Journal of Vascular Research, 46 (3). pp. 209-217.
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Background and Aims: Osteoprotegerin (OPG) has been associated with abdominal aortic aneurysm (AAA) expansion. Angiotensin II (AngII) receptor blockade has been shown to reduce OPG expression in human AAA tissue. Interaction between vascular AngII and OPG was further examined using cell culture and the AngII-infused ApoE-/- mouse AAA model. The ability of peroxisome proliferator-activated receptor-gamma (PPARgamma) activation to target OPG as potential therapy for AAA was also investigated. Methods and Results: Human aortic smooth muscle cells (AoSMC) exposed to AngII exhibited dose-dependent increase in the production OPG. A 3-fold increase in suprarenal aortic concentration of OPG was observed in AngII-infused ApoE-/- mice. AngII type 1 receptor expression in human AAA tissue, and AoSMC in vitro, was stimulated up 4-fold in the presence of OPG. This effect in AoSMC was counteracted in the presence of the PPARgamma ligand, pioglitazone. Addition of PPARgamma ligand to cultured human AAA explant reduced OPG secretion by 60% and tissue concentration of OPG and metalloproteinase 9 by 2- and 3-fold, respectively. Administration of pioglitazone to AngII-infused ApoE-/- mice significantly reduced aortic concentrations of OPG and metalloproteinase 9. Conclusions: These data support an interaction between AngII and OPG in aneurysm formation. Activation of PPARgamma may have a role in treatment of AAA.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||abdominal aortic aneurysm; angiotensin II; AT1 receptor; PPAR-y; smooth muscle cells; osteoprotegerin; metalloproteinase 9|
|Funders:||National Institute of Health, NHMRC, National Heart Foundation of Australia|
|Date Deposited:||20 Sep 2009 23:37|
|FoR Codes:||11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%|
|Citation Count from Web of Science||