Iron alters valvular interstitial cell function and is associated with calcification in aortic stenosis

Area of Science:

• Cardiovascular Research
• Biomedical Science
• Pathology

Background:

• Aortic valve stenosis (AS) is a common valvulopathy characterized by inflammation, extracellular matrix (ECM) remodeling, and calcification.
• Intraleaflet hemorrhage is associated with AS progression, but the underlying mechanisms remain unclear.

Purpose of the Study:

• To investigate valvular iron accumulation in relation to pathological changes in AS.
• To determine the effects of iron on valvular interstitial cells (VICs), including iron uptake and responses.

Main Methods:

• Perls' staining to detect valvular iron accumulation in aortic valve sections.
• Quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression in iron-containing regions.
• Assessment of iron uptake and iron-induced responses in VICs.

Main Results:

• Valvular iron accumulation increased with the extent of calcification.
• Iron-rich valve areas showed increased expression of genes involved in ECM remodeling and calcification.
• VICs demonstrated iron uptake, leading to increased proliferation and decreased elastin production.

Conclusions:

• Iron accumulation in aortic valves, potentially from hemorrhage, can be taken up by VICs.
• Iron uptake by VICs in a pro-inflammatory environment promotes VIC proliferation, ECM remodeling, and calcification.
• These findings suggest a mechanism by which iron uptake by VICs contributes to AS progression.