Low and Unsteady Shear Stresses Upregulate Calcification Response of the Aortic Valve Leaflets

2011 ◽  
Author(s):  
Swetha Rathan ◽  
Choon Hwai Yap ◽  
Elizabeth Morris ◽  
Sivakkumar Arjunon ◽  
Hanjoong Jo ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Mechanical Loading ◽  
Causes Of Death ◽  
Fluid Shear Stress ◽  
Degenerative Disease ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Cellular Processes ◽  
Aortic Valve Leaflets

Aortic Valve (AV) calcification is a degenerative disease that results in AV sclerosis and is one of the major causes of death. AV is subjected to mechanical conditions such as fluid shear stress, transvalvular pressure and membrane tension1. Normal hemodynamic conditions constantly renew and remodel the valve, whereas altered mechanical loading has been implicated to be the cause of AV disease2. Studies have shown that adverse hemodynamics such as hypertension and altered shear stress can cause tissue inflammation that leads to calcification and stenosis3, 4, and ultimately result in valve failure. However, the molecular and cellular processes that lead to calcification are not very well understood.

Experimental Technique of Measuring Dynamic Fluid Shear Stress on the Aortic Surface of the Aortic Valve Leaflet

2011 ◽  
Vol 133 (6) ◽  
Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Steady Flow ◽  
Fluid Shear Stress ◽  
Shear Stresses ◽  
Straight Tube ◽  
Valve Leaflet ◽  
Fluid Shear ◽  
Valve Model

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5dyn/cm2) but elevated to its peak during mid to late systole at about 18–20 dyn/cm2. Low magnitude shear stress (<5dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.

Effects of Fluid Shear Stress on Endothelial Cell Invasion Into Three-Dimensional Matrices

2007 ◽  
Author(s):  
Hojin Kang ◽  
Kayla J. Bayless ◽  
Roland Kaunas
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Invasion ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Shear Stresses ◽  
Collagen Gels ◽  
Fluid Shear

We have previously developed a cell culture model to study the effects of angiogenic factors, such as sphingosine-1-phosphate (S1P), on the invasion of endothelial cells into the underlying extracellular matrix. In addition to biochemical stimuli, vascular endothelial cells are subjected to fluid shear stress due to blood flow. The present study is aimed at determining the effects of fluid shear stress on endothelial cell invasion into collagen gels. A device was constructed to apply well-defined fluid shear stresses to confluent human umbilical vein endothelial cells (HUVECs) seeded on collagen gels. Fluid shear stress induced significant increases in cell invasion with a maximal induction at ∼5 dyn/cm2. These results provide evidence that fluid shear stress is a significant stimulus for endothelial cell invasion and may play a role in regulating angiogenesis.

The Fluid Shear Stress Distribution on the Membrane of Leukocytes in the Microcirculation

2003 ◽  
Vol 125 (5) ◽  
pp. 628-638 ◽  
Author(s):  
Masako Sugihara-Seki ◽  
Geert W. Schmid-Scho¨nbein
Keyword(s):  
Shear Stress ◽  
Stress Distribution ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Shear Stress Distribution ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Stress Gradients ◽  
Freely Suspended ◽  
Microvessel Wall

Recent in-vivo and in-vitro evidence indicates that fluid shear stress on the membrane of leukocytes has a powerful control over several aspects of their cell function. This evidence raises a question about the magnitude of the fluid shear stress on leukocytes in the circulation. The flow of plasma on the surface of a leukocyte at a very low Reynolds number is governed by the Stokes equation for the motion of a Newtonian fluid. We numerically estimated the distribution of fluid shear stress on a leukocyte membrane in a microvessel for the cases when the leukocyte is freely suspended, as well as rolling along or attached to a microvessel wall. The results indicate that the fluid shear stress distribution on the leukocyte membrane is nonuniform with a sharp increase when the leukocyte makes membrane attachment to the microvessel wall. In a microvessel (10 μm diameter), the fluid shear stress on the membrane of a freely suspended leukocyte (8 μm diameter) is estimated to be several times larger than the wall shear stress exerted by the undisturbed Poiseuille flow, and increases on an adherent leukocyte up to ten times. High temporal stress gradients are present in freely suspended leukocytes in shear flow due to cell rotation, which are proportional to the local shear rate. In comparison, the temporal stress gradients are reduced on the membrane of leukocytes that are rolling or firmly adhered to the endothelium. High temporal gradients of shear stress are also present on the endothelial wall. At a plasma viscosity of 1 cPoise, the peak shear stresses for suspended and adherent leukocytes are of the order of 10 dyn/cm2 and 100 dyn/cm2, respectively.

Design and Validation of a Novel Bioreactor to Expose Aortic Valve Leaflets to Side-Specific Shear Stress

2011 ◽  
Author(s):  
Ling Sun ◽  
Nalini M. Rajamannan ◽  
Philippe Sucosky
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Fluid Shear Stress ◽  
Left Ventricular ◽  
Calcific Aortic Valve Disease ◽  
Aortic Valve Leaflets ◽  
Left Ventricular Outflow ◽  
Pulsatile Shear Stress ◽  
Plate Geometry

Calcific aortic valve disease (CAVD), the most common aortic valve disorder, is characterized by an accumulation of calcium on the valve leaflets that contributes to the obstruction of the left ventricular outflow and progressive heart failure. CAVD follows an active process presumably triggered by atherogenic risk factors and hemodynamic cues1,2. Resulting from the relative motion between the deforming leaflets and the surrounding blood flow, fluid shear stress is an important component of the valve hemodynamic environment. The ventricular surface of the leaflets is exposed to a unidirectional pulsatile shear stress, while the aortic surface experiences a bidirectional oscillatory shear stress3. The characterization of the effects of shear stress on valvular pathogenesis, which requires the replication of the native valvular shear stress in the laboratory setting, has been hampered by this hemodynamic complexity. In an effort to address this challenge, the goal of this study was to design and validate a novel apparatus capable of exposing simultaneously but independently both surfaces of aortic valve leaflets to native side-specific shear stress. The device based on a cone-and-plate geometry was validated with respect to its ability to expose each surface of aortic valve leaflets to its native, time-varying shear stress waveform, while maintaining the tissue under sterile conditions for 96 hours.

Contribution of Hemodynamic Shear Stress Magnitude and Frequency Abnormalities to Calcific Aortic Valve Disease Pathogenesis

2013 ◽  
Author(s):  
Ling Sun ◽  
Philippe Sucosky
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Fluid Shear Stress ◽  
Ex Vivo ◽  
Valve Disease ◽  
Molecular Signaling ◽  
Fluid Shear ◽  
Calcific Aortic Valve Disease ◽  
Hemodynamic Shear Stress

Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between atherogenic risk factors, molecular signaling networks and hemodynamic cues. While our earlier work demonstrated that progressive alterations in fluid shear stress (FSS) on the fibrosa could trigger valvular inflammation [1], the mechanisms of CAVD pathogenesis secondary to side-specific FSS abnormalities are poorly understood. Supported by our previous studies, we hypothesize that valve leaflets are sensitive to both WSS magnitude and pulsatility and that abnormalities in either promote CAVD development. This study aims at elucidating ex vivo the contribution of isolated and combined alterations in FSS magnitude and pulsatility to valvular calcification.

scholarly journals Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1366-1374 ◽  
Author(s):  
JL Moake ◽  
NA Turner ◽  
NA Stathopoulos ◽  
L Nolasco ◽  
JD Hellums
Keyword(s):  
Shear Stress ◽  
Platelet Aggregation ◽  
Fluid Shear Stress ◽  
Thrombus Formation ◽  
Adenosine Diphosphate ◽  
Shear Stresses ◽  
Fluid Shear ◽  
Von Willebrand ◽  
Induced Aggregation

Abstract Fluid shear stress in arteries and arterioles partially obstructed by atherosclerosis or spasm may exceed the normal time-average level of 20 dyne/cm2. In vitro, at fluid shear stresses of 30 to 60 dyne/cm2 applied for 30 seconds, platelet aggregation occurs. At these shear stresses, either large or unusually large von Willebrand factor (vWF) multimers in the suspending fluid exogenous to the platelets mediates aggregation. Adenosine diphosphate (ADP) is also required and, in these experiments, was released from the platelets subjected to shear stress. At 120 dyne/cm2, the release of endogenous platelet vWF multimers can substitute for exogenous large or unusually large vWF forms in mediating aggregation. Endogenous released platelet vWF forms, as well as exogenous large or unusually large vWF multimers, must bind to both glycoproteins Ib and the IIb/IIIa complex to produce aggregation. Shear- induced aggregation is the result of shear stress alteration of platelet surfaces, rather than of shear effects on vWF multimers. It is mediated by either large plasma-type vWF multimers, endogenous released platelet vWF forms, or unusually large vWF multimers derived from endothelial cells, requires ADP, and is not inhibited significantly by aspirin. This type of aggregation may be important in platelet thrombus formation within narrowed arterial vessels, and may explain the limited therapeutic utility of aspirin in arterial thrombosis.

Development of Microfluidic Chips to Study the Effects of Shear Stress on Cell Functions

2010 ◽  
Author(s):  
Jianbin Wang ◽  
Jinseok Heo ◽  
Susan Z. Hua
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Cellular Systems ◽  
Shear Stresses ◽  
Microfluidic Chips ◽  
Fluid Shear ◽  
Cell Functions ◽  
Culture Cells ◽  
Wide Range ◽  
On Chip

Fluid shear stress has profound effect on many cell functions, including proliferation, migration, transport, and gene expression. Cellular systems such as endothelial cells in heart artery and epithelial cells in kidney tubule are constantly subject to fluid flow. We have developed a series of microfluidic chips that generate a wide range and modes of shear stresses within a perfusion chamber, enabling us to culture cells on chip and examine the effects of shear stress on cell growth and cell functions.

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