The Congenital Bicuspid Aortic Valve Can Experience Fluid Shear Stresses Associated With Sclerosis

Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Swetha Rathan ◽  
Gowthami Tamilselvan ◽  
Nikolay V. Vasilyev ◽  
...  

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2].

Author(s):  
Choon Hwai Yap ◽  
Neelakantan Saikrishnan ◽  
Gowthami Tamilselvan ◽  
Ajit P. Yoganathan

Aortic valve calcification is a degenerative disease with high prevalence, especially amongst the elderly, and is a major cause of morbidity and mortality. Ex vivo experiments has shown that aortic valve leaflets are sensitive to their mechanical environment in a magnitude dependent manner. Fluid shear stresses, specifically, has been shown to affect inflammatory and remodeling responses relevant to aortic valve calcification [1,2]. Consequently, it has been proposed that the phenomenon of diseased calcium nodules developing exclusively on the aortic surface as opposed to the ventricular surface is due to the exposure of the aortic surface to disturbed shear stresses, whereas undisturbed shear stresses on the ventricular surface do not trigger calcification [3,4]. Additionally, it has been observed that the non-coronary leaflet of the AV is more susceptible to calcification, which is hypothesized to be due to reduced shear stresses from the lack of diastolic coronary flow [5].


2020 ◽  
Vol 11 ◽  
Author(s):  
Arsenii Zabirnyk ◽  
Maria del Mar Perez ◽  
Marc Blasco ◽  
Kåre-Olav Stensløkken ◽  
Miguel D. Ferrer ◽  
...  

Background: No pharmacological treatment exists to prevent or stop the calcification process of aortic valves causing aortic stenosis. The aim of this study was to develop a robust model of induced calcification in whole aortic valve leaflets which could be suitable for studies of the basic mechanisms and for testing potentially inhibitory drugs.Methods: Pig hearts were obtained from a commercial abattoir. The aortic valve leaflets were dissected free and randomized between experimental groups. Whole leaflets were cultured in individual wells. Two growth media were used for cultivation: standard growth medium and an antimyofibroblastic growth medium. The latter was employed to inhibit contraction of the leaflet into a ball-like structure. Calcification was induced in the growth medium by supplementation with an osteogenic medium. Leaflets were cultivated for four weeks and medium was changed every third day. To block calcification, the inhibitor SNF472 (a formulation of the hexasodium salt of myo-inositol hexaphosphate hexasodium salt) was used at concentrations between 1 and 100 µM. After cultivation for four weeks the leaflets were snap frozen in liquid nitrogen and kept at −80 °C until blind assessment of the calcium amount in leaflets by inductively coupled plasma optical emission spectroscopy. For statistical analysis, a Kruskal–Wallis test with Dunn’s post-test was applied.Results: Osteodifferentiation with calcium accumulation was in principle absent when standard medium was used. However, when the antimyofibroblastic medium was used, a strong calcium accumulation was induced (p = 0.006 compared to controls), and this was blocked in a dose-dependent manner by the calcification inhibitor SNF472 (p = 0.008), with an EC50 of 3.3 µM.Conclusion: A model of experimentally induced calcification in cultured whole leaflets from porcine aortic valves was developed. This model can be useful for studying the basic mechanisms of valve calcification and to test pharmacological approaches to inhibit calcification.


2006 ◽  
Vol 186 (2) ◽  
pp. 342-349 ◽  
Author(s):  
Franklin Liu ◽  
Courtney A. Coursey ◽  
Cairistine Grahame-Clarke ◽  
Robert R. Sciacca ◽  
Anna Rozenshtein ◽  
...  

Hypertension ◽  
2013 ◽  
Vol 61 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Shinichi Iwata ◽  
Cesare Russo ◽  
Zhezhen Jin ◽  
Joseph E. Schwartz ◽  
Shunichi Homma ◽  
...  

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