Changes of endocan and dermatan sulfate are associated with biomechanical properties of abdominal aortic wall during aneurysm expansion and rupture

Metschl, S., Bruder, L., Paloschi, V., Jakob, K., Reutersberg, B., Reeps, C., Maegdefessel, L., Gee, M.W., Eckstein, H.-H., Pelisek, J.

doi:10.1055/a-1772-0574

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Professur für Mechanik auf Höchstleistungsrechnern (Prof. Gee)

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Title:: Changes of endocan and dermatan sulfate are associated with biomechanical properties of abdominal aortic wall during aneurysm expansion and rupture
Document type:: Zeitschriftenaufsatz
Author(s):: Metschl, S., Bruder, L., Paloschi, V., Jakob, K., Reutersberg, B., Reeps, C., Maegdefessel, L., Gee, M.W., Eckstein, H.-H., Pelisek, J.
Abstract:: Background and aims: The study aimed to assess the potential of proteoglycans (PG) 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 (ELISA), 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, Col3), chondroitin sulfate (CS), and dermatan sulfate (DS) were significantly increased compared to 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 to eAAA. Tissue β-stiffness was higher in rAAA compared to 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 =0.02), tissue endocan correlated with α-stiffness (r=0.340; p<0.01). Signaling pathways in AAA were associated with ECM synthesis and VSMC proliferation. In particular, Src family kinases, PDGF- and EGF-related proteins seem to be involved. Conclusions: 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:: Thrombosis and Haemostasis
Year:: 2022
Fulltext / DOI:: doi:10.1055/a-1772-0574
Status:: Verlagsversion / published
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