Angiotensin II receptor antagonism reduces transforming growth factor beta and smad signaling in thoracic aortic aneurysm

Nataatmadja, Maria, West, Jennifer, Prabowo, Sulistiana and West, Malcolm (2013) Angiotensin II receptor antagonism reduces transforming growth factor beta and smad signaling in thoracic aortic aneurysm. Ochsner Journal, 13 1: 42-48.

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Author Nataatmadja, Maria
West, Jennifer
Prabowo, Sulistiana
West, Malcolm
Title Angiotensin II receptor antagonism reduces transforming growth factor beta and smad signaling in thoracic aortic aneurysm
Journal name Ochsner Journal   Check publisher's open access policy
ISSN 1524-5012
Publication date 2013
Sub-type Article (original research)
Volume 13
Issue 1
Start page 42
End page 48
Total pages 7
Place of publication New Orleans, LA, U.S.A.
Publisher Ochsner Clinic
Collection year 2014
Language eng
Subject 2700 Medicine
Abstract Background: The expression of transforming growth factor beta (TGF-β) and Smad3 regulates extracellular matrix homeostasis and inflammation in aortic aneurysms. The expression of Smad3 depends on signaling by angiotensin II (AngII) receptor pathways through TGF-β receptor-dependent and -independent pathways. Methods: To determine the expression of AngII type 1 (AT1R) and type 2 receptors (AT2R), TGF-β, and Smad3 in thoracic aortic aneurysms, we performed immunohistochemistry testing on tissue and cultured cells derived from subjects with Marfan syndrome (MFS) and bicuspid aortic valve (BAV) malformation and from normal aortas of subjects who were organ donors. Results: MFS and BAV aneurysm tissue showed enhanced accumulation of TGF-β and Smad3 in vascular smooth muscle cells (VSMCs) and in inflammatory cells in the subintimal layer and tunica media. The normal aortic wall exhibited minimal TGF-β and Smad3 staining. Cultured VSMCs from MFS and BAV samples showed nuclear Smad3 and strong cytoplasmic TGF-β expression in the cytoplasmic vesicles. In control cells, Smad3 was located mainly in the cytoplasm, and weak cytoplasmic TGF-β was distributed with a pattern similar to that of the aneurysm-derived cells. Compared to normal aorta cells, AT1R and AT2R expression was increased in both aneurysm types. Treatment of cultured VSMCs with the AT21R antagonist losartan caused both reduced TGF-β vesicle localization and nuclear expression of Smad3. Conclusions: Increased TGF-β and Smad3 expression in aneurysm tissue and cultured VSMCs is consistent with aberrant TGF-β expression and the activation of Smad3 signaling. Losartan-mediated reduction in TGF-β expression and the cytoplasmic localization of Smad3 support a role for AT1R antagonism in the inhibition of aneurysm progression.
Keyword Aneurysm
Aorta
Immunohistochemistry
Smad3 protein
Transforming growth factor beta
Vascular smooth muscle
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Created: Tue, 21 Jan 2014, 15:44:31 EST by Matthew Lamb on behalf of School of Medicine