University of Oulu

Endothelial factors in the pathogenesis of aortic valve stenosis

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Author: Peltonen, Tuomas1,2,3,4,5
Organizations: 1University of Oulu, Faculty of Medicine, Institute of Biomedicine, Department of Pharmacology and Toxicology
2University of Oulu, Faculty of Medicine, Institute of Biomedicine, Department of Physiology
3University of Oulu, Faculty of Medicine, Institute of Clinical Medicine, Department of Surgery
4University of Oulu, Faculty of Medicine, Institute of Diagnostics, Department of Pathology
5University of Oulu, Biocenter Oulu
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.4 MB)
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Language: English
Published: 2008
Publish Date: 2008-12-09
Thesis type: Doctoral Dissertation
Defence Note: Academic dissertation to be presented, with the assent of the Faculty of Medicine of the University of Oulu, for public defence in Auditorium 101 A of the Faculty of Medicine (Aapistie 5 A), on December 19th, 2008, at 12 noon
Reviewer: Docent Ken Lindstedt
Docent Timo Savunen


Calcified aortic valve disease represents a spectrum of disease spanning from mild aortic valve sclerosis to severe aortic valve stenosis (AS), being an actively regulated disease process and showing some hallmarks of atherosclerosis. The calcified aortic valve lesion develops endothelial injury and is characterized by inflammation, lipid accumulation, renin-angiotensin system activation and fibrosis. There is no approved pharmacological treatment available in AS.

This study was aimed to characterize gene expression of endothelial factors in aortic valves in patients representing different stages of calcified aortic valve disease to reveal new targets for pharmacological interventions in AS. Aortic valves obtained from 75 patients undergoing valve replacement surgery were studied. Expression of natriuretic peptides (ANP, BNP and CNP), their processing enzymes (corin and furin), natriuretic receptors (NPR-A, NPR-B and NPR-C), endothelin-1 (ET-1), endothelin converting enzyme-1 (ECE-1), endothelin receptors A and B (ETA and ETB), and apelin pathway (apelin and its receptor APJ) was characterized by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry.

AS was characterized by distinct downregulation of gene expression of CNP, its processing enzyme furin and the target receptor NPR-B. Furthermore, increased amount of ET-1 and its target receptor ETA as well as imbalance between ETA and ETB receptors and downregulated endothelial nitric oxide synthase (eNOS) gene expression were observed. Finally, gene expression of apelin and APJ receptor were significantly upregulated in stenotic valves when compared to controls in combination with disequilibrium between expression of angiotensin II receptors AT1 and AT2. The study provides a better understanding of molecular echanisms associated with calcific aortic valve disease and suggest potential targets for novel therapeutic interventions.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 978-951-42-8988-0
ISBN Print: 978-951-42-8987-3
Issue: 997
Copyright information: © University of Oulu, 2008. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.