A role for Iron in Aortic Valve Stenosis
Although it has been recently shown that intraleaflet hemorrhage is associated with aortic stenosis (AS) progression, the possible pathophysiology of iron accumulation in the valve and the role of valve interstitial cells (VIC) has remained hitherto unexplored. in this study we show that:
1 - Non-heme iron accumulates in AS in relation to the degree of calcification and is associated with an increased expression of genes that promote extracellular matrix remodeling and calcification.
2 - VIC can take up and accumulate iron, and iron transporters are regulated by pathways with a major impact on AS pathophysiology.
3 - Iron induced VIC proliferation and decreased elastin production.
Taken together, these results provide mechanistic insights and suggest potential pathways linking for example intraleaflet hemorrhage to a maladaptive response to injury and valvular calcification.