Cardiovascular Fluid Mechanics Laboratory

Aortic Valve Mechanobiology

The aortic valve (AV) is located between the left ventricle and the aorta. It consists of three leaflets that open during systole to allow the passage of oxygenated blood from the ventricle into the aorta, and close during diastole to prevent the blood from flowing back into the ventricle. Thus, the AV experiences a dynamic mechanical environment with significant variations in pressure, bending stress, and shear stress on either side. These loads lead to constant renewal and remodelling of the valve. Our previous research has shown that an altered mechanical environment triggers altered remodeling and inflammation responses in the AV.

av-mech-environment
The aortic valve is subjected to a complex mechanical environment, which plays very important roles in valvular health.

Calcific AV disease (CAVD) is a major cause of mortality worldwide, and typically treated through surgical valve repair or replacement. Due to the lack of understanding of the molecular mechanisms causing AV disease, appropriate non-surgical treatment strategies have not been well developed. Ongoing research at the CFM Lab aims to characterize biological valvular responses to both physiological stimuli and hemodynamic changes in the environment of the valve. This will provide insights into normal valve function and pathology and lead to the design of ex vivo bioreactors for the preconditioning and evaluation of tissue engineered heart valves.

Cyclic stretch bioreactor (left) and cone and plate shear stress bioreactor (right)
Cyclic stretch bioreactor (left) and cone and plate shear stress bioreactor (right)

Select Publications

  1. Arjunon S et al. Aortic Valve: Mechanical Environment and Mechanobiology. Ann Biomed Eng. 2013; 41(7): 1331-46.
  2. Balachandran K et al. Elevated cyclic stretch alters matrix remodeling in aortic valve cusps: implications for degenerative aortic valve disease. Am J Physiol Heart Circ Physiol. 2009; 296(3): H756-64.
  3. Balachandran K et al. Elevated Cyclic Stretch Induces Aortic Valve Calcification in a Bone Morphogenic Protein-Dependent Manner. Am J Pathol. 2010; 177(1): 49-57.
  4. Rathan, S., A. Yoganathan and W. O’Neill (Accepted Oct 2013). “Role of Inorganic Pyrophosphate in Aortic Valve Calcification.” Journal of Heart Valve Disease.
  5. Sucosky, P et al. Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4- and TGF-{beta}1-Dependent Pathway. Arterioscler Thromb Vasc Biol. 2009;  29(2): 254-260.