Biomechanical Analysis of Embryonic Atrioventricular Valvulogenesis

Author(s):  
Philip R. Buskohl ◽  
Russell A. Gould ◽  
Jonathan T. Butcher

Heart valve development is directed by a complex interaction of molecular and mechanical cues[1]. Both molecular and mechanical based approaches are needed to clarify these relationships. Many technologies exist for the former, but the short length scale and super-compliant material properties of embryonic valve tissue make conventional mechanical testing techniques ineffective. The pipette aspiration technique has been a useful tool in cell mechanics[2] and has recently been applied to adult valve leaflets[3]. Geometric effects of thin, planar tissues however compromise the utility of aspiration based measurements. Herein, we utilize pipette aspiration and a novel uni-axial micro-tensile testing apparatus to quantify the biomechanical evolution of avian embryonic heart valves. We then relate biomechanical stiffening to changes in underlying structural composition.

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
YenChun Ho ◽  
Xin Geng ◽  
Rohan Varshney ◽  
Jang Kim ◽  
Sandeep Surbrahmanian ◽  
...  

Background: Heart valves regulate the unidirectional forward flow and prevent retrograde backflow of blood during the cardiac cycle. Cardiac valve disease (CVD) is observed in approximately 2.5% of the general population and the incidence increases to ~10% in elderly people. Patients with severe CVD require surgery and effective pharmacological treatments are currently not available. PROX1 is a transcription factor that regulates the development of lymphatic, venous, and lymphovenous valves (vascular valves). We identified that PROX1 is also expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 regulates cardiac valve development and disease is not known. Method and Results: We have discovered that mice lacking Prox1 in their VECs ( Prox1 ΔVEC ) develop enlarged aortic and mitral valves in which the expression of proteoglycans is increased (control, N=10; Prox1 ΔVEC , N=9, p <0.05). Echocardiography revealed moderate to severe stenosis of aortic valves of Prox1 ΔVEC mice (control, N=5; Prox1 ΔVEC , N=9, p <0.05). PROX1 regulates the expression of the transcription factor FOXC2 in the vascular valves. Similarly, we have found that the expression of FOXC2 is downregulated in the VECs of Prox1 ΔVEC mice. Specific knockdown of FOXC2 in VECs results in the thickening of aortic valves (control, N=10; shFoxc2 ΔVEC , N=8, p <0.05). Furthermore, restoration of FOXC2 expression in VECs ( Foxc2 OE-VEC ) ameliorates the thickening of the aortic valves of Prox1 ΔVEC mice ( Prox1 ΔVEC , N=9; Foxc2 OE-VEC ; Prox1 ΔVEC , N=8, p <0.05). We have also determined that the expression of platelet-derived growth factor-B ( Pdgfb ) is increased in the valve tissue of Prox1 ΔVEC mice and in PROX1 deficient sheep mitral valve VECs (MVECs) (siCtrl , N=4; siProx1 , N=4, p <0.05). Additionally, hyperactivation of PDGF-B signaling in mice results in a phenotype that is similar to Prox1 ΔVEC mice (control , N=4; Pdgfb GOF , N=3, p <0.05). Conclusion: Together these data suggest that PROX1 maintains the extracellular matrix composition of cardiac valves by regulating the expressions of FOXC2 and PDGF-B in VECs.


Circulation ◽  
2000 ◽  
Vol 102 (Supplement 3) ◽  
pp. III-50-III-55 ◽  
Author(s):  
G. Steinhoff ◽  
U. Stock ◽  
N. Karim ◽  
H. Mertsching ◽  
A. Timke ◽  
...  

Author(s):  
Marco Stevanella ◽  
Emiliano Votta ◽  
Massimo Lemma ◽  
Carlo Antona ◽  
Alberto Redaelli

The tricuspid valve (TV) is the right atrio-ventricular valve. The most common TV disease is secondary or functional tricuspid regurgitation (FTR), an important complication of left-sided valvular heart lesions, which frequently persists after mitral and aortic valve operations. FTR is associated with high mortality and morbidity and requires surgical intervention, the preferential solution being TV repair through techniques such as annuloplasty performed during left heart surgery. However, significant residual regurgitation persists or recurs in 10% to 20% after annuloplasty, thus highlighting the incomplete understanding of the underlying mechanisms and the need for deeper insight into TV pathophysiology. At this purpose finite element models (FEMs) could be adopted, as suggested by their effective application to the biomechanical analysis of left heart valves. However, while for those several data are available regarding morphology and tissue mechanical properties, such information is missing for the TV, making it difficult to implement a FEM of the TV.


2020 ◽  
Vol 21 (17) ◽  
pp. 6330
Author(s):  
Grzegorz J. Lis ◽  
Andrzej Dubrowski ◽  
Maciej Lis ◽  
Bernard Solewski ◽  
Karolina Witkowska ◽  
...  

Aortic valve interstitial cells (VICs) constitute a heterogeneous population involved in the maintenance of unique valvular architecture, ensuring proper hemodynamic function but also engaged in valve degeneration. Recently, cells similar to telocytes/interstitial Cajal-like cells described in various organs were found in heart valves. The aim of this study was to examine the density, distribution, and spatial organization of a VIC subset co-expressing CD34 and PDGFRα in normal aortic valves and to investigate if these cells are associated with the occurrence of early signs of valve calcific remodeling. We examined 28 human aortic valves obtained upon autopsy. General valve morphology and the early signs of degeneration were assessed histochemically. The studied VICs were identified by immunofluorescence (CD34, PDGFRα, vimentin), and their number in standardized parts and layers of the valves was evaluated. In order to show the complex three-dimensional structure of CD34+/PDGFRα+ VICs, whole-mount specimens were imaged by confocal microscopy, and subsequently rendered using the Imaris (Bitplane AG, Zürich, Switzerland) software. CD34+/PDGFRα+ VICs were found in all examined valves, showing significant differences in the number, distribution within valve tissue, spatial organization, and morphology (spherical/oval without projections; numerous short projections; long, branching, occasionally moniliform projections). Such a complex morphology was associated with the younger age of the subjects, and these VICs were more frequent in the spongiosa layer of the valve. Both the number and percentage of CD34+/PDGFRα+ VICs were inversely correlated with the age of the subjects. Valves with histochemical signs of early calcification contained a lower number of CD34+/PDGFRα+ cells. They were less numerous in proximal parts of the cusps, i.e., areas prone to calcification. The results suggest that normal aortic valves contain a subpopulation of CD34+/PDGFRα+ VICs, which might be involved in the maintenance of local microenvironment resisting to pathologic remodeling. Their reduced number in older age could limit the self-regenerative properties of the valve stroma.


2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
E Rieder ◽  
MT Kasimir ◽  
G Seebacher ◽  
E Wolner ◽  
P Simon ◽  
...  

Author(s):  
Siyao Huang ◽  
Hsiao-Ying Shadow Huang

Heart valves are inhomogeneous microstructure with nonlinear anisotropic properties and constantly experience different stress states during cardiac cycles. However, how tissue-level mechanical forces can translate into altered cellular stress states remains unclear, and associated biomechanical regulation in the tissue has not been fully understood. In the current study, we use an image-based finite element method to investigate factors contributing the stress distributions at both tissue- and cell-levels inside the healthy heart valve tissues. Effects of tissue microstructure, inhomogeneity, and anisotropic material property at different diastole states are discussed to provide a better understanding of structure-mechanics-property interactions, which alters tissue-to-cell stress transfer mechanisms in heart valve tissue. To the best of the authors’ knowledge, this is the first study reporting on the evolution of stress fields at both the tissue- and cellular-levels in valvular tissue, and thus contributes toward refining our collective understanding of valvular tissue micromechanics while providing a computational tool enabling further study of valvular cell-tissue interactions.


Sensors ◽  
2021 ◽  
Vol 21 (9) ◽  
pp. 2923
Author(s):  
Florian Scheible ◽  
Raphael Lamprecht ◽  
Marion Semmler ◽  
Alexander Sutor

The voice producing process is a complex interplay between glottal pressure, vocal folds, their elasticity and tension. The material properties of vocal folds are still insufficiently studied, because the determination of material properties in soft tissues is often difficult and connected to extensive experimental setups. To shed light on this less researched area, in this work, a dynamic pipette aspiration technique is utilized to measure the elasticity in a frequency range of 100–1000 Hz. The complex elasticity could be assessed with the phase shift between exciting pressure and tissue movement. The dynamic pipette aspiration setup has been miniaturized with regard to a future invivo application. The techniques were applied on 3 different porcine larynges 4 h and 1 d postmortem, in order to investigate the deterioration of the tissue over time and analyze correlation in elasticity values between vocal fold pairs. It was found that vocal fold pairs do have different absolute elasticity values but similar trends. This leads to the assumption that those trends are more important for phonation than having same absolute values.


2014 ◽  
Vol 18 (4 (72)) ◽  
Author(s):  
O. H. Popadynets ◽  
O. V. Sahan ◽  
N. M. Dubyna

The heart has two similar each to other in structure inlet (atriaventricular) and two outlet (ventricularvascular) valvular apparatuses. The mitral (bicuspid) and tricuspid valves are atriaventricular heart valves. The aortic and pulmonary valves are ventricular-vascular heart valves. The valvular apparatus of the heart is the complex system, which includes: the fibrous ring, cusps, tendinous cords and papillary muscles. The last two components are characteristic for the atriaventricular valvular apparatuses and they are absent in the ventricular-vascular valvular apparatuses. The valvular apparatuses of aorta and pulmonary trunk have the fibrous rings, the wall of aorta/pulmonary trunk, semilunar cusps. The laying of the valvular apparatuses begins on early stages of embryonic development and finishes before the beginning of fetal period of the prenatal ontogenesis. The normal function of the heart and human body is dependent on the complex interaction of all components of the valvular apparatus of the heart. Many discussions of the development, structure with peculiari ties of the blood supply, the age changes remain in the fundamental investigations. The modern diagnostic and medical apparatuses, the possibilities of the modern methods of investigations require from scientists the renewal of the known facts about the valvular apparatuses of the heart. They might be useful as the theoretical and practical background which will deepen the understanding of the pathogenesis and the quality of heart diseases treatment. 


2001 ◽  
Vol 281 (6) ◽  
pp. H2604-H2611 ◽  
Author(s):  
K. L. Weind ◽  
D. R. Boughner ◽  
L. Rigutto ◽  
C. G. Ellis

To maintain tissue oxygenation, normal aortic valves contain a vascular bed where tissue thickness is greatest. Avascular “living” tissue-engineered heart valves have been proposed, yet little information exists regarding the magnitude of valve tissue metabolic activity or oxygen requirements. We therefore set out to measure the oxygen diffusivity (Do2 ) and oxygen consumption (V˙o 2) of seven porcine aortic valve cusps in vitro at 37°C using a chamber with a Clark oxygen sensor. MeanDo2 and V˙o 2 were 1.06 × 10−5 cm2/s and 3.05 × 10−5 · ml O2 · ml tissue−1 · s−1, respectively. When modeled as a three-layered structure by using these values and a boundary condition of 100 mmHg at both surfaces, the average aortic cusp predicted a central mean Po 2 of 27 mmHg (range of 0–50 mmHg). The Do2 value obtained was similar to that found for other vascular structures, but because our studies were carried out in vitro, theV˙o 2 measurements may be lower than that required by the functioning valves. These values provide an initial understanding of the oxygen supply possible from the cusp surfaces and the oxygen needs of the tissue.


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