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Thromb Haemost 2022; 122(09): 1513-1523
DOI: 10.1055/a-1772-0574
Cellular Signalling and Proteolysis

Changes in Endocan and Dermatan Sulfate Are Associated with Biomechanical Properties of Abdominal Aortic Wall during Aneurysm Expansion and Rupture

Susanne Metschl
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Lukas Bruder
3   Mechanics and High Performance Computing Group, Technical University of Munich, Munich, Germany
,
Valentina Paloschi 
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Katharina Jakob
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
,
Benedikt Reutersberg
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
4   Department of Vascular Surgery, University Hospital Zurich, Zurich, Switzerland
,
Christian Reeps
5   Department of Visceral, Thoracic, and Vascular Surgery, Medizinische Fakultät an der TU-Dresden, Dresden, Germany
,
Lars Maegdefessel
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Michael Gee
3   Mechanics and High Performance Computing Group, Technical University of Munich, Munich, Germany
,
Hans-Henning Eckstein
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Jaroslav Pelisek 
1   Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
4   Department of Vascular Surgery, University Hospital Zurich, Zurich, Switzerland
› Author Affiliations Funding This study was funded by the German Research Foundation (Deutsche Forschungs-gemeinschaft, DFG) (project number GZ: RE3146/1-1 and GE2254/1-1).
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Abstract

Background and Aims The study aimed to assess the potential of proteoglycans (PGs) and collagens as serological biomarkers in the abdominal aortic aneurysm (AAA). Furthermore, we investigated the underlying mechano-biological interactions and signaling pathways.

Methods Tissue and serum samples from patients with ruptured AAA (rAAA; n = 29), elective AAA (eAAA; n = 78), and healthy individuals (n = 8) were evaluated by histology, immunohistochemistry, and enzyme-linked immunosorbent assay, and mechanical properties were assessed by tensile tests. Regulatory pathways were determined by membrane-based sandwich immunoassay.

Results In AAA samples, collagen type I and III (Col1 and Col3), chondroitin sulfate, and dermatan sulfate (DS) were significantly increased compared with controls (3.0-, 3.2-, 1.3-, and 53-fold; p < 0.01). Col1 and endocan were also elevated in the serum of AAA patients (3.6- and 6.0-fold; p < 0.01), while DS was significantly decreased (2.5-fold; p < 0.01). Histological scoring showed increased total PGs and focal accumulation in rAAA compared with eAAA. Tissue β-stiffness was higher in rAAA compared with eAAA (2.0-fold, p = 0.02). Serum Col1 correlated with maximum tensile force and failure tension (r = 0.448 and 0.333; p < 0.01, and r = 0.02), tissue endocan correlated with α-stiffness (r = 0.340; p < 0.01). Signaling pathways in AAA were associated with extracellular matrix synthesis and vascular smooth muscle cell proliferation. In particular, Src family kinases and platelet-derived growth factor- and epidermal growth factor-related proteins seem to be involved.

Conclusion Our findings reveal a structural association between collagen and PGs and their response to changes in mechanical loads in AAA. Particularly Col1 and endocan reflect the mechano-biological conditions of the aortic wall also in the patient's serum and might serve for AAA risk stratification.

Keywords

abdominal aortic aneurysm - biomarkers - proteoglycans - endocan - dermatan sulfate

Supplementary Material



Publication History

Received: 19 September 2021

Accepted: 12 February 2022

Accepted Manuscript online:
15 February 2022

Article published online:
18 May 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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