Iron alters valvular interstitial cell function and is associated with calcification in aortic stenosis.
Aortic valve stenosis (AS) is the most common valvulopathy and is characterized by inflammation, extracellular matrix (ECM) remodelling and calcification, causing a narrowing of the valve and the consequential obstruction of the cardiac outflow. Although intraleaflet haemorrhage is associated with AS progression, the mechanisms involved are not known. The aims of this study were to identify valvular iron in relation to pathological changes associated with AS and the effects on valvular interstitial cells (VIC) in terms of iron uptake and iron-induced responses.



Valvular iron accumulation was detected by Perls' staining on aortic valve sections and shown to increase with the extent of calcification. Furthermore, qRT-PCR analysis revealed that iron-containing valve regions exhibited increased expression of genes involved in ECM remodelling and calcification. In addition, we demonstrate that iron transporters are regulated by pathways with major impact on AS and that VIC can take up and accumulate iron, which resulted in increased proliferation and decreased elastin production.



Iron, which may accumulate in the aortic valve by means of intraleaflet haemorrhages, can be taken up by VIC in a pro-inflammatory environment and actively contribute to VIC proliferation, ECM remodelling and calcification. These findings suggest a possible mechanism through which iron uptake by VIC may favour AS progression.
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Andres
A
Laguna-Fernandez
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Miguel
M
Carracedo
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Gregoire
G
Jeanson
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Edit
E
Nagy
Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Per
P
Eriksson
Institut National de la Santé et de la Recherche Médicale U1148, Paris, France.
Giuseppina
G
Caligiuri
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Franco-Cereceda
Department of Medicine, Karolinska Institutet, Stockholm, Sweden magnus.back@ki.se.|Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
Magnus
M
Bäck
D001021:Aortic Valve; D001024:Aortic Valve Stenosis; D002114:Calcinosis; D006349:Heart Valve Diseases; D006801:Humans; D007501:Iron
D007501:Iron
Aortic valve stenosis; Calcification; Elastin; Iron