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.

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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