What modulates the aortic valve interstitial cell phenotype?

Age-related, degenerative aortic valve disease is of great concern for the current aging population, and the only current treatment option is replacement, necessitating open-chest surgery. While the initial disease mechanism may involve the endothelial cells that sheath the valve leaflets, there is strong evidence supporting the notion that it is in fact a malfunction of the robust interstitial cells within the leaflet tissue that perpetuate the disease through a presently unclear sequence of events. In this article, recent data are discussed regarding mechanobiology of the interstitial cell, with particular focus on modulation of the phenotype and subsequent biosynthetic function. Moreover, speculation of potential mechanisms that may ultimately lead to degenerative aortic valve disease are discussed.