Abstract 13341: Spheroid Mineralized Microparticles in Calcific Aortic Stenosis are Produced by Valve Interstitial Cells: Implication of Mechanical Strain and Rhoa
Backgound: Calcific aortic valve stenosis (AS) is the most frequent valvular heart disease. The aortic valve is exposed to a complex mechanical environment, which involves cyclic strain and shear stress. There is mounting evidence suggesting that increased mechanical strain may contribute to the mineralization of aortic valves. However, the mechanism underlying this process is largely unknown.
Methods: interstitial valve cells (VICs) were isolated and studied under mechanical strain conditions. Mineralization of VICs was studied by using transmission electron microscopy and energy dispersive x-ray (EDX) analyses. Human bicuspid aortic valves were examined as a model relevant to increase mechanical strain.
Results: Cyclical mechanical strain increased mineralization of VICs by several-folds. Scanning electron microscopy (SEM) and EDX analyses revealed that mechanical strain promoted the formation of mineralized spheroid particles, which coalesced into larger diffuse plate-like structure at the surface of apoptotic VICs. Mineralization was accompanied by the expression of ENPP1. Inhibition of ENPP1 greatly reduced mechanical strain-induced apoptosis and mineralization of VICs cultures. Through several lines of evidence we then showed that mechanical strain promoted cargo vesicle export containing ENPP1 to the plasma membrane through RhoA pathway. Studies conducted in human bicuspid aortic valve BAV with SEM and EDX revealed the presence of spheroid-mineralized structures along with the expression of ENPP1 in areas of high mechanical strain.
Conclusion: Hence this study suggests that the spheroid-mineralized microparticles observed in human stenotic aortic valves are likely derived from VICs. Also, we highlighted that mechanical strain is an important trigger leading to the formation of mineralized microparticles through a RhoA dependent pathway.
- © 2013 by American Heart Association, Inc.