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

Metschl, Susanne; Bruder, Lukas; Paloschi, Valentina; Jakob, Katharina; Reutersberg, Benedikt; Reeps, Christian; Maegdefessel, Lars; Gee, Michael; Eckstein, Hans-Henning; Pelisek, Jaroslav

doi:10.1055/a-1772-0574

2022

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Title:: Changes in Endocan and Dermatan Sulfate Are Associated with Biomechanical Properties of Abdominal Aortic Wall during Aneurysm Expansion and Rupture.
Document type:: Journal Article
Author(s):: Metschl, Susanne; Bruder, Lukas; Paloschi, Valentina; Jakob, Katharina; Reutersberg, Benedikt; Reeps, Christian; Maegdefessel, Lars; Gee, Michael; Eckstein, Hans-Henning; Pelisek, Jaroslav
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.
Journal title abbreviation:: Thromb Haemost
Year:: 2022
Journal volume:: 122
Journal issue:: 9
Pages contribution:: 1513-1523
Fulltext / DOI:: doi:10.1055/a-1772-0574
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/35170008
Print-ISSN:: 0340-6245
TUM Institution:: Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie (Prof. Eckstein); Professur für Vaskuläre Biologie (Prof. Maegdefessel)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie (Prof. Eckstein)Professur für Vaskuläre Biologie (Prof. Maegdefessel)2022

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie (Prof. Eckstein)2022