Extracellular matrix remodeling and organization in developing and diseased aortic valves

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Pathology

Background:

• Heart valve disease is a major global health issue with poorly understood pathogenesis.
• Genetic factors suggest a developmental origin for valve disease.
• Regulation of extracellular matrix (ECM) and valvular interstitial cell (VIC) distribution in mature valves is not well-defined.

Purpose of the Study:

• To investigate ECM organization and VIC distribution during late valvulogenesis.
• To compare normal valve development with diseased bicuspid aortic valves (BAVs) from pediatric patients.

Main Methods:

• Histochemistry, immunohistochemistry, and electron microscopy were employed.
• Analysis of late valvulogenesis in chicken and mouse models.
• Examination of explanted stenotic BAVs from pediatric patients.

Main Results:

• Mature valve ECM organization is conserved across species and develops postnatally.
• ECM stratification and VIC compartmentalization occur with decreased cell proliferation.
• Diseased BAVs show disrupted ECM, disorganized collagens and proteoglycans, and fragmented elastic fibers without increased cell proliferation.

Conclusions:

• Normal heart valve development requires precise spatiotemporal coordination of ECM organization and VIC compartmentalization.
• These developmental processes are disrupted in pediatric patients with diseased BAVs.
• Disruption of developmental coordination contributes to valve disease pathogenesis.