Universität zu Köln

Niepmann, Sven Thomas, Steffen, Eva, Zietzer, Andreas, Adam, Matti ORCID: 0000-0002-6990-8135, Nordsiek, Julia, Gyamfi-Poku, Isabella, Piayda, Kerstin, Sinning, Jan-Malte, Baldus, Stephan, Kelm, Malte ORCID: 0000-0003-0060-1052, Nickenig, Georg, Zimmer, Sebastian and Quast, Christine (2019). Graded murine wire-induced aortic valve stenosis model mimics human functional and morphological disease phenotype. Clin. Res. Cardiol., 108 (8). S. 847 - 857. HEIDELBERG: SPRINGER HEIDELBERG. ISSN 1861-0692

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Abstract

Aortic valve stenosis (AS) is the most common valve disease requiring therapeutic intervention. Even though the incidence of AS has been continuously rising and AS is associated with significant morbidity and mortality, to date, no medical treatments have been identified that can modify disease progression. This unmet medical need is likely attributed to an incomplete understanding of the molecular mechanism driving disease development. To investigate the pathophysiology leading to AS, reliable and reproducible animal models that mimic human pathophysiology are needed. We have tested and expanded the protocols of a wire-injury induced AS mouse model. For this model, coronary wires were used to apply shear stress to the aortic valve cusps with increasing intensity. These protocols allowed distinction of mild, moderate and severe wire-injury. Upon moderate or severe injury, AS developed with a significant increase in aortic valve peak blood flow velocity. While moderate injury promoted solitary AS, severe-injury induced mixed aortic valve disease with concomitant mild to moderate aortic regurgitation. The changes in aortic valve function were reflected by dilation and hypertrophy of the left ventricle, as well as a decreased left ventricular ejection fraction. Histological analysis revealed the classic hallmarks of human disease with aortic valve thickening, increased macrophage infiltration, fibrosis and calcification. This new mouse model of AS promotes functional and morphological changes similar to moderate and severe human AS. It can be used to investigate the pathomechanisms contributing to AS development and to test novel therapeutic strategies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Niepmann, Sven Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Steffen, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Zietzer, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Adam, Matti UNSPECIFIED orcid.org/0000-0002-6990-8135 UNSPECIFIED Nordsiek, Julia UNSPECIFIED UNSPECIFIED UNSPECIFIED Gyamfi-Poku, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Piayda, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Sinning, Jan-Malte UNSPECIFIED UNSPECIFIED UNSPECIFIED Baldus, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelm, Malte UNSPECIFIED orcid.org/0000-0003-0060-1052 UNSPECIFIED Nickenig, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Zimmer, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Quast, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-145042
DOI:	10.1007/s00392-019-01413-1
Journal or Publication Title:	Clin. Res. Cardiol.
Volume:	108
Number:	8
Page Range:	S. 847 - 857
Date:	2019
Publisher:	SPRINGER HEIDELBERG
Place of Publication:	HEIDELBERG
ISSN:	1861-0692
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL FACTORS; PROGRESSION; CALCIFICATION; INFLAMMATION; REPLACEMENT; HEART Multiple languages Cardiac & Cardiovascular Systems Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14504