Calcific Aortic Valve Disease Is Associated with Layer-Specific Alterations in Collagen Architecture

Area of Science:

• Cardiovascular Biology
• Biomaterials Science
• Tissue Engineering

Background:

• Disorganization of the valve extracellular matrix (ECM) is a hallmark of calcific aortic valve disease (CAVD).
• Little is known about the ECM microarchitecture in CAVD, despite its influence on tissue behavior.

Purpose of the Study:

• To quantify spatially heterogeneous changes in collagen microarchitecture in CAVD using advanced imaging.
• To investigate layer-specific alterations in collagen fiber characteristics in healthy versus diseased human aortic valves.

Main Methods:

• Second Harmonic Generation microscopy for collagen imaging.
• Image quantification to analyze fiber characteristics (number, width, density, alignment).
• Immunohistochemical staining for lysyl oxidase expression.

Main Results:

• Significant collagen fiber changes in CAVD occurred in the spongiosa layer, with a >2-fold increase in fiber number, width, and density.
• The fibrosa layer showed minimal changes in fiber number, width, density, or alignment, but fibers became significantly shorter.
• Increased lysyl oxidase expression was localized in the diseased fibrosa.

Conclusions:

• Findings reveal a complex collagen enrichment and arrangement in CAVD, differing from previous analyses.
• Altered fiber architecture in CAVD may influence pathobiological events and mechanical properties.
• ECM microarchitecture characterization can inform the design of scaffolds for heart valve tissue engineering.