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The Extracellular Matrix Signature in Vein Graft Disease
Birgit Kahle1, Claudia Schmidtke2, Nicolas Hunzelmann3
1Department of Dermatology, University of Lübeck, Lübeck, Germany.
The Canadian Journal of Cardiology
|March 2, 2016
Summary
Vein graft disease involves significant changes in extracellular matrix composition, particularly collagen and elastin. Targeting collagen cross-links may offer a new therapeutic strategy for this condition.
Area of Science:
- Biomedical Engineering
- Cardiovascular Surgery
- Biochemistry
Background:
- Vein graft disease is a significant challenge in cardiac revascularization surgery.
- The fibrotic nature of vein graft disease involves extracellular matrix accumulation, but detailed analysis is lacking.
- Collagen cross-link alterations are characteristic of organ fibrosis, prompting investigation in vein graft disease.
Purpose of the Study:
- To conduct a comprehensive analysis of collagen and elastin composition in vein graft disease.
- To investigate the role of collagen cross-links and their modifying enzymes in vein graft disease.
- To assess changes in the elastin to collagen ratio and fibrillin expression in diseased vein grafts.
Main Methods:
- Histology and amino acid analysis were used to quantify collagen, elastin, and their cross-links.
- Quantitative real-time PCR (SYBR Green) assessed the expression of collagen-modifying enzymes.
- Immunohistochemistry and quantitative real-time PCR analyzed fibrillin expression.
Main Results:
- Diseased vein grafts exhibited increased collagen and intermediate collagen cross-links, indicating new collagen synthesis.
- Elevated levels of mature hydroxylysine aldehyde-derived cross-links, typical of skeletal tissues, were found.
- A reduced elastin/collagen ratio was observed, associated with increased fibrillin-1 expression and upregulation of lysyl hydroxylase 2 and lysyl oxidase.
Conclusions:
- Vein graft disease is characterized by substantial alterations in extracellular matrix composition.
- The modified collagen cross-link pattern and reduced elastin/collagen ratio may contribute to increased vein graft stiffness.
- Hydroxylysine aldehyde-derived cross-links could decrease collagen degradability, suggesting collagen cross-links as a potential therapeutic target.
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