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- Dokumenttyp:
- Journal Article
- Autor(en):
- Metschl, Susanne; Bruder, Lukas; Paloschi, Valentina; Jakob, Katharina; Reutersberg, Benedikt; Reeps, Christian; Maegdefessel, Lars; Gee, Michael; Eckstein, Hans-Henning; Pelisek, Jaroslav
- Titel:
- Changes in Endocan and Dermatan Sulfate Are Associated with Biomechanical Properties of Abdominal Aortic Wall during Aneurysm Expansion and Rupture.
- 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.
- Zeitschriftentitel:
- Thromb Haemost
- Jahr:
- 2022
- Band / Volume:
- 122
- Heft / Issue:
- 9
- Seitenangaben Beitrag:
- 1513-1523
- Volltext / DOI:
- doi:10.1055/a-1772-0574
- PubMed:
- http://view.ncbi.nlm.nih.gov/pubmed/35170008
- Print-ISSN:
- 0340-6245
- TUM Einrichtung:
- Klinik und Poliklinik für Vaskuläre und Endovaskuläre Chirurgie (Prof. Eckstein); Professur für Vaskuläre Biologie (Prof. Maegdefessel)
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