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J Am Coll Cardiol, 2004; 44:1859-1866, doi:10.1016/j.jacc.2004.07.054
© 2004 by the American College of Cardiology Foundation
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Induction of local angiotensin II-producing systems in stenotic aortic valves

Satu Helske, MD*, Ken A. Lindstedt, PhD*, Mika Laine, MD, PhD{dagger}, Mikko Mäyränpää, MD*, Kalervo Werkkala, MD, PhD{ddagger}, Jyri Lommi, MD, PhD§, Heikki Turto, MD, PhD§, Markku Kupari, MD, PhD§ and Petri T. Kovanen, MD, PhD*,*

* Wihuri Research Institute, Helsinki, Finland
{dagger} Minerva Institute for Medical Research, Helsinki, Finland
{ddagger} Divisions of Cardiothoracic Surgery
§ Cardiology, Helsinki University Central Hospital, Helsinki, Finland



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Figure 1 Local angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT-1R) activities are increased in stenotic aortic valves. (A) ACE autoradiography images of a normal and a stenotic aortic valve. (B) Quantitative analysis of ACE autoradiography levels in normal (n = 11) and stenotic (n = 11) aortic valves. (C) Quantitative analysis of AT-1R autoradiography showed 5.5-fold increase (p < 0.05) in the level of AT-1R in stenotic aortic valves (n = 11) compared with control valves (n = 11). Results are mean values ± SD. *p < 0.05; ***p < 0.001.

 


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Figure 2 Angiotensin-converting enzyme (ACE) messenger ribonucleic acid (mRNA) expression is higher in stenotic aortic valves (n = 84) than in control valves (n = 11). Individual data points and medians are shown.

 


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Figure 3 Chymase messenger ribonucleic acid (mRNA) expression is increased in stenotic aortic valves (n = 84) over that of control valves (n = 11). Lines denote medians.

 


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Figure 4 Mast cell (MC) numbers are higher in stenotic than in normal aortic valves. (A) The total number of MCs (cells/mm2) in stenotic (n = 86) and normal (n = 11) aortic valves. (B) The number of chymase-containing MCs in stenotic (n = 11) and normal (n = 11) aortic valves. Lines indicate medians.

 


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Figure 5 Immunostaining of mast cells (MC) in normal (A) and stenotic (B) aortic valves. (A) Section of a normal aortic valve showing a few MCs (arrows) in a subendothelial location. (B) Section of a stenotic aortic valve demonstrating MC distribution throughout the leaflet and association of MCs with the calcified lesions of the valves (one arrow).

 


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Figure 6 A resting mast cell (MC) in a control valve (A) and an activated mast cell in a stenotic aortic valve (B). (C) Quantification of the degree of MC degranulation (i.e., activation) in normal (n = 11) and stenotic (n = 11) aortic valves. Lines denote medians.

 


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Figure 7 Adjacent sections of an aortic valve showing colocalization (arrows) of macrophages (A) and angiotensin-converting enzyme (ACE) (B). Control staining with unspecific goat immunoglobulin G shows no immunoreactivity (C).

 




 
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