Universität zu Köln

Freise, Christian ORCID: 0000-0003-2602-226X, Schaefer, Betti, Bartosova, Maria, Bayazit, Aysun, Bauer, Ulrike, Pickardt, Thomas ORCID: 0000-0003-0019-6325, Berger, Felix, Rasmussen, Lars Melholt ORCID: 0000-0001-5795-4794, Jensen, Pia Sondergaard, Laube, Guido, Mencarelli, Francesca, Arbeiter, Klaus, Buescher, Rainer, Habbig, Sandra, Moeller, Kristina, Kirchner, Marietta, Schaefer, Franz, Schmitt, Claus Peter and Querfeld, Uwe (2019). Arterial tissue transcriptional profiles associate with tissue remodeling and cardiovascular phenotype in children with end-stage kidney disease. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Chronic kidney disease (CKD) greatly increases the risk for cardiovascular disease (CVD). However, molecular mechanisms underlying CKD-induced arterial remodeling are largely unknown. We performed a systematic analysis of arterial biopsies from children with stage 5 predialysis CKD participating in the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4 C) study. For comparison, we studied biopsies from children without CKD, coronary bypass vessels from adults with atherosclerotic coronary heart disease without CKD and aortic sections of subtotally nephrectomized rats. In pediatric CKD patients, gene expression was correlated to the cardiovascular phenotype assessed by surrogate end-points. The arterial calcium content correlated with the intima-media thickness (IMT) of biopsied vessels from pediatric CKD patients, was markedly increased compared to biopsies from children without CKD and comparable to adult coronary bypass patients. Significant transcriptional changes included ECM components, pro-calcifying factors, and physiological calcification inhibitors; most were highly accordant with changes observed in adults with atherosclerosis and in uremic rats. Individual gene expression levels were significantly associated with the left ventricular mass index and carotid intima media thickness. Thus, inflammatory processes (TNF, IL-10), calcification inhibitors (CA2), the Wnt-pathway (FGF-2) and foremost, ECM components (HMGA1, VNN1, VCAN), impact pathobiological responses in arteries from children with CKD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Freise, Christian UNSPECIFIED orcid.org/0000-0003-2602-226X UNSPECIFIED Schaefer, Betti UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartosova, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Bayazit, Aysun UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauer, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Pickardt, Thomas UNSPECIFIED orcid.org/0000-0003-0019-6325 UNSPECIFIED Berger, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Rasmussen, Lars Melholt UNSPECIFIED orcid.org/0000-0001-5795-4794 UNSPECIFIED Jensen, Pia Sondergaard UNSPECIFIED UNSPECIFIED UNSPECIFIED Laube, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Mencarelli, Francesca UNSPECIFIED UNSPECIFIED UNSPECIFIED Arbeiter, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Buescher, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Habbig, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Moeller, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kirchner, Marietta UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Franz UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmitt, Claus Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Querfeld, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-135059
DOI:	10.1038/s41598-019-46805-5
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR CALCIFICATION; OSTEOBLASTIC DIFFERENTIATION; REFERENCE VALUES; EXPRESSION; INHIBITORS; CORONARY; MEDIA; BLOOD; CKD Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13505