Universität zu Köln

Kahle, Birgit, Schmidtke, Claudia, Hunzelmann, Nicolas, Bartels, Claus, Sievers, Hans H., Steenbock, Heiko, Reinhardt, Dieter P. and Brinckmann, Juergen (2016). The Extracellular Matrix Signature in Vein Graft Disease. Can. J. Cardiol., 32 (8). NEW YORK: ELSEVIER SCIENCE INC. ISSN 1916-7075

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Abstract

Background: Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen crosslinks are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease. Methods: Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. Results: Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1. Conclusions: Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kahle, Birgit UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidtke, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunzelmann, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartels, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Sievers, Hans H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Steenbock, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Dieter P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-268254
DOI:	10.1016/j.cjca.2015.11.014
Journal or Publication Title:	Can. J. Cardiol.
Volume:	32
Number:	8
Date:	2016
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1916-7075
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TELOPEPTIDE LYSYL HYDROXYLASE; COLLAGEN CROSS-LINKS; NEOINTIMA FORMATION; TGF-BETA; FIBROSIS; ATHEROSCLEROSIS; IDENTIFICATION; FIBRILLINS; MECHANISMS; EXPRESSION Multiple languages Cardiac & Cardiovascular Systems Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26825