title: Hemodynamic and cellular response feedback in calcific aortic valve disease.
abstract: This review highlights aspects of calcific aortic valve disease that encompass the entire range of aortic valve disease progression from initial cellular changes to aortic valve sclerosis and stenosis, which can be initiated by changes in blood flow (hemodynamics) and pressure across the aortic valve. Appropriate hemodynamics is important for normal valve function and maintenance, but pathological blood velocities and pressure can have profound consequences at the macroscopic to microscopic scales. At the macroscopic scale, hemodynamic forces impart shear stresses on the surface of the valve leaflets and cause deformation of the leaflet tissue. As discussed in this review, these macroscale forces are transduced to the microscale, where they influence the functions of the valvular endothelial cells that line the leaflet surface and the valvular interstitial cells that populate the valve extracellular matrix. For example, pathological changes in blood flow-induced shear stress can cause dysfunction, impairing their homeostatic functions, and pathological stretching of valve tissue caused by elevated transvalvular pressure can activate valvular interstitial cells and latent paracrine signaling cytokines (eg, transforming growth factor-β1) to promote maladaptive tissue remodeling. Collectively, these coordinated and complex interactions adversely impact bulk valve tissue properties, feeding back to further deteriorate valve function and propagate valve cell pathological responses. Here, we review the role of hemodynamic forces in calcific aortic valve disease initiation and progression, with focus on cellular responses and how they feed back to exacerbate aortic valve dysfunction.
authors.affiliation: Department of Chemical and Biological Engineering, The Biofrontiers Institute, University of Colorado, Boulder, CO 80303, USA.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Gould
authors.forename: Suthan
authors.initials: S
authors.lastname: Srigunapalan
authors.forename: Craig A
authors.initials: CA
authors.lastname: Simmons
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000166:cytology / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D000082882:Bicuspid Aortic Valve Disease; D002114:Calcinosis / Q000473:pathology* / Q000503:physiopathology; D009202:Cardiomyopathies / Q000473:pathology* / Q000503:physiopathology; D006330:Heart Defects, Congenital / Q000473:pathology* / Q000503:physiopathology; D006349:Heart Valve Diseases / Q000473:pathology* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*
keywords: effective orifice area; endothelial dysfunction; valve tissue remodeling; valvular endothelial cells; valvular interstitial cells