Mechanobiology in Cardiovascular Disease Management: Potential Strategies and Current Needs

Atkins, Samantha K.; McNally, Andrew; Sucosky, Philippe

doi:10.3389/fbioe.2016.00079

Cited by 9 publications

(4 citation statements)

References 31 publications

(30 reference statements)

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“…The possible causality between these two facts has been partially but rigorously provided by ex vivo studies conducted in our laboratory, which have demonstrated the ability of the stress abnormalities generated in the disease-prone convexity of the LR-BAV aorta to trigger aortic medial remodeling via MMP-dependent pathways and the absence of any significant remodeling in response to the hemodynamics of the disease-protected concavity (Atkins and Sucosky, 2014 ; Atkins et al, 2014 , 2016b ; Sucosky, 2014 ). In this context, the data presented in this study suggests that the elucidation of the shear stress environment in BAV AAs might be critical toward the development of improved clinical guidelines for the management of BAV patients (Atkins et al, 2016a ).…”

Section: Discussionmentioning

confidence: 96%

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

2017

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The bicuspid aortic valve (BAV) is a major risk factor for secondary aortopathy such as aortic dilation. The heterogeneous BAV morphotypes [left-right-coronary cusp fusion (LR), right-non-coronary cusp fusion (RN), and left-non-coronary cusp fusion (LN)] are associated with different dilation patterns, suggesting a role for hemodynamics in BAV aortopathogenesis. However, assessment of this theory is still hampered by the limited knowledge of the hemodynamic abnormalities generated by the distinct BAV morphotypes. The objective of this study was to compare experimentally the hemodynamics of a normal (i.e., non-dilated) ascending aorta (AA) subjected to tricuspid aortic valve (TAV), LR-BAV, RN-BAV, and NL-BAV flow. Tissue BAVs reconstructed from porcine TAVs were subjected to physiologic pulsatile flow conditions in a left-heart simulator featuring a realistic aortic root and compliant aorta. Phase-locked particle image velocimetry experiments were carried out to characterize the flow in the aortic root and in the tubular AA in terms of jet skewness and displacement, as well as mean velocity, viscous shear stress and Reynolds shear stress fields. While all three BAVs generated skewed and asymmetrical orifice jets (up to 1.7- and 4.0-fold increase in flow angle and displacement, respectively, relative to the TAV at the sinotubular junction), the RN-BAV jet was out of the plane of observation. The LR- and NL-BAV exhibited a 71% increase in peak-systolic orifice jet velocity relative to the TAV, suggesting an inherent degree of stenosis in BAVs. While these two BAV morphotypes subjected the convexity of the aortic wall to viscous shear stress overloads (1.7-fold increase in maximum peak-systolic viscous shear stress relative to the TAV-AA), the affected sites were morphotype-dependent (LR-BAV: proximal AA, NL-BAV: distal AA). Lastly, the LR- and NL-BAV generated high degrees of turbulence in the AA (up to 2.3-fold increase in peak-systolic Reynolds shear stress relative to the TAV) that were sustained from peak systole throughout the deceleration phase. This in vitro study reveals substantial flow abnormalities (increased jet skewness, asymmetry, jet velocity, turbulence, and shear stress overloads) in non-dilated BAV aortas, which differ from those observed in dilated aortas but still coincide with aortic wall regions prone to dilation.

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Section: Discussionmentioning

confidence: 96%

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

2017

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“…While all these flow abnormalities may play different roles in BAV disease, they all impact the tissue via the interfacial fluid shear stress imposed on the endothelium. This observation combined with the established ability of vascular endothelial cells to sense and respond to changes in WSS magnitude, directionality and frequency through biological expression of cytokines, modulation of ion channels and smooth muscle cell signaling (Chiu and Chien, 2011;Lieu et al, 2004;Passerini et al, 2003) have suggested the key role played by WSS in BAV disease (S. K. Atkins et al, 2016a). Despite the compelling evidence for the involvement of local flow abnormalities in the pathogenesis of BAV aortopathy, the existence of a hemodynamic etiology is still questionable as it is uncertain whether the reported flow abnormalities were due primarily to the valve morphology, the pre-existence of dilation in BAV patients, or anatomic differences between different patient cohorts.…”

Section: Introductionmentioning

confidence: 98%

Simulations of morphotype-dependent hemodynamics in non-dilated bicuspid aortic valve aortas

Cao

Atkins

McNally

et al. 2017

Journal of Biomechanics

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Bicuspid aortic valves (BAVs) generate flow abnormalities that may promote aortopathy. While positive helix fraction (PHF) index, flow angle (θ), flow displacement (d) and wall shear stress (WSS) exhibit abnormalities in dilated BAV aortas, it is unclear whether those anomalies stem from the abnormal valve anatomy or the dilated aorta. Therefore, the objective of this study was to quantify the early impact of different BAV morphotypes on aorta hemodynamics prior to dilation. Fluid-structure interaction models were designed to quantify standard peak-systolic flow metrics and temporal WSS characteristics in a realistic non-dilated aorta connected to functional tricuspid aortic valve (TAV) and type-I BAVs. While BAVs generated increased helicity (PHF>0.68) in the middle ascending aorta (AA), larger systolic flow skewness (θ>11.2°) and displacement (d>6.8mm) relative to the TAV (PHF=0.51; θ<5.5°; d<3.3mm), no distinct pattern was observed between morphotypes. In contrast, WSS magnitude and directionality abnormalities were BAV morphotype- and site-dependent. Type-I BAVs subjected the AA convexity to peak-systolic WSS overloads (up to 1014% difference vs. TAV). While all BAVs increased WSS unidirectionality on the proximal AA relative to the TAV, the most significant abnormality was achieved by the BAV with left-right-coronary cusp fusion on the wall convexity (up to 0.26 decrease in oscillatory shear index vs. TAV). The results indicate the existence of strong hemodynamic abnormalities in non-dilated type-I BAV AAs, their colocalization with sites vulnerable to dilation and the superior specificity of WSS metrics over global hemodynamic metrics to the valve anatomy.

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“… Fischer et al, 2020 ; Lee et al, 2019 ), cardiovascular disease (e.g. Atkins et al, 2016 ; Takahashi et al, 2013 ) and hypertension (e.g. Bloodworth et al, 2015 ; Dieffenbach et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Design of a 3D printed, motorized, uniaxial cell stretcher for microscopic and biochemical analysis of mechanotransduction

2021

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Cells respond to mechanical cues from their environment through a process of mechanosensing and mechanotransduction. Cell stretching devices are important tools to study the molecular pathways responsible for cellular responses to mechanobiological processes. We describe the development and testing of a uniaxial cell stretcher that has applications for microscopic as well as biochemical analyses. By combining simple fabrication techniques with adjustable control parameters, the stretcher is designed to fit a variety of experimental needs. The stretcher can be used for static and cyclic stretching. As a proof of principle, we visualize stretch induced deformation of cell nuclei via incremental static stretch, and changes in IEX1 expression via cyclic stretching. This stretcher is easily modified to meet experimental needs, inexpensive to build, and should be readily accessible for most laboratories with access to 3D printing.

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Mechanobiology in Cardiovascular Disease Management: Potential Strategies and Current Needs

Cited by 9 publications

References 31 publications

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

Morphotype-Dependent Flow Characteristics in Bicuspid Aortic Valve Ascending Aortas: A Benchtop Particle Image Velocimetry Study

Simulations of morphotype-dependent hemodynamics in non-dilated bicuspid aortic valve aortas

Design of a 3D printed, motorized, uniaxial cell stretcher for microscopic and biochemical analysis of mechanotransduction

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