• aortoseptal angle
• computational fluid dynamics
• discrete subaortic stenosis
• fibrosis
• hemodynamics
• left ventricular outflow tract
• wall shear stress

• R01 HL140305 NHLBI NIH HHS

• aortic valve
• bicuspid aortic valve
• fluid-structure interaction
• hemodynamics
• stress
• stretch

• Aortic Valve/abnormalities
• Aortic Valve/physiopathology
• Aortic Valve Stenosis/etiology
• Bicuspid Aortic Valve Disease
• Calcinosis/physiopathology
• Cardiomyopathies/physiopathology
• Heart Valve Diseases/physiopathology
• Humans
• Tricuspid Valve/abnormalities
• Tricuspid Valve/physiopathology

• aorta
• aortopathy
• bicuspid aortic valve
• hemodynamics
• particle image velocimetry

AIM: To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects.

METHODS: Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography.

RESULTS: Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively).

CONCLUSION: The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA.

• Bicuspid aortic valve
• Fluid shear stress
• Aortopathy
• Remodeling
• Matrix metalloproteinases

The bicuspid aortic valve (BAV) is the most common form of inheritable cardiac defect. Although this abnormality may still achieve normal valvular function, it is often associated with secondary valvular and aortic complications such as calcific aortic valve disease and aortic dilation. The clinical significance and economic burden of BAV disease justify the need for improved clinical guidelines and more robust therapeutic modalities, which address the root-cause of those pathologies. Unfortunately, the etiology of BAV valvulopathy and aortopathy is still a debated issue. While the BAV anatomy and its secondary complications have been linked historically to a common genetic root, recent advances in medical imaging have demonstrated the existence of altered hemodynamics near BAV leaflets prone to calcification and BAV aortic regions vulnerable to dilation. The abnormal mechanical stresses imposed by the BAV on its leaflets and on the aortic wall could be transduced into cell-mediated processes, leading ultimately to valvular calcification and aortic medial degeneration. Despite increasing evidence for this hemodynamic etiology, the demonstration of the involvement of mechanical abnormalities in the pathogenesis of BAV disease requires the investigation of causality between the blood flow environment imposed on the leaflets and the aortic wall and the local biology, which has been lacking to date. This editorial discusses the different hypothetical etiologies of BAV disease with a particular focus on the most recent advances in cardiovascular imaging, flow characterization techniques and tissue culture methodologies that have provided new evidence in support of the hemodynamic theory.

• Aortopathy
• Valvulopathy
• Hemodynamics
• Bicuspid aortic valve
• Shear stress