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Updated: Aug 29, 2025

A Method to Study the Correlation Between Local Collagen Structure and Mechanical Properties of Atherosclerotic Plaque Fibrous Tissue
Published on: November 11, 2022
Collagen Molecular Damage is a Hallmark of Early Atherosclerosis Development
Kelly A Smith1, Allen H Lin1,2, Alexander H Stevens1
1Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, 84112, USA.
Abstract:
Remodeling of extracellular matrix proteins underlies the development of cardiovascular disease. Herein, we utilized a novel molecular probe, collagen hybridizing peptide (CHP), to target collagen molecular damage during atherogenesis. The thoracic aorta was dissected from ApoE-/- mice that had been on a high-fat diet for 0-18 weeks. Using an optimized protocol, tissues were stained with Cy3-CHP and digested to quantify CHP with a microplate assay. Results demonstrated collagen molecular damage, inferred from Cy3-CHP fluorescence, was a function of location and time on the high-fat diet. Tissue from the aortic arch showed a significant increase in collagen molecular damage after 18 weeks, while no change was observed in tissue from the descending aorta. No spatial differences in fluorescence were observed between the superior and inferior arch tissue. Our results provide insight into the early changes in collagen during atherogenesis and present a new opportunity in the subclinical diagnosis of atherosclerosis.
Insights
Collagen molecular damage increases over time in the aortic arch of mice on a high-fat diet. This finding, using collagen hybridizing peptide (CHP), offers potential for early atherosclerosis diagnosis.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
- Molecular Biology
Background:
- Extracellular matrix protein remodeling is crucial in cardiovascular disease development.
- Atherogenesis involves progressive changes in the aorta.
- Early detection of molecular damage is key for cardiovascular disease intervention.
Purpose of the Study:
- To investigate collagen molecular damage during atherogenesis using a novel molecular probe.
- To assess the impact of diet duration and location on collagen damage in the aorta.
- To explore the potential of collagen hybridizing peptide (CHP) for subclinical atherosclerosis diagnosis.
Main Methods:
- Dissection of thoracic aorta from ApoE-/- mice fed a high-fat diet for 0-18 weeks.
- Staining tissues with Cy3-labeled collagen hybridizing peptide (CHP).
- Quantification of CHP fluorescence using a microplate assay to infer collagen damage.
Main Results:
- Collagen molecular damage was dependent on both location within the aorta and duration of the high-fat diet.
- Significant collagen damage was observed in the aortic arch after 18 weeks.
- No significant changes in collagen damage were detected in the descending aorta.
Conclusions:
- Collagen hybridizing peptide (CHP) can detect early molecular damage in collagen during atherogenesis.
- Aortic arch collagen is particularly susceptible to diet-induced damage.
- This approach presents a novel method for the subclinical diagnosis of atherosclerosis.
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