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Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves.

ABSTRACT: Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves. During fibrotic valve disease, leaflet thickening due to abnormal extracellular matrix is likely to reduce regional oxygen availability. To assess the impact of low oxygen levels on valve behaviour, whole leaflet organ cultures were created to induce leaflet hypoxia. These studies revealed a loss of layer stratification and elevated levels of hypoxia inducible factor 1-alpha in both aortic and mitral valve hypoxic groups. Mitral valves also exhibited altered expression of angiogenic factors in response to low oxygen environments when compared with normoxic groups. Hypoxia affected aortic and mitral valves differently, and mitral valves appeared to show a stenotic, rheumatic phenotype accompanied by significant cell death. These results indicate that hypoxia could be a factor in mid to late valve disease progression, especially with the reduction in chondromodulin-1 expression shown by hypoxic mitral valves.

SUBMITTER: Sapp MC

PROVIDER: S-EPMC5221519 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves.

Sapp Matthew C MC Krishnamurthy Varun K VK Puperi Daniel S DS Bhatnagar Saheba S Fatora Gabrielle G Mutyala Neelesh N Grande-Allen K Jane KJ

Journal of the Royal Society, Interface 20161201 125

Tissue oxygenation often plays a significant role in disease and is an essential design consideration for tissue engineering. Here, oxygen diffusion profiles of porcine aortic and mitral valve leaflets were determined using an oxygen diffusion chamber in conjunction with computational models. Results from these studies revealed the differences between aortic and mitral valve leaflet diffusion profiles and suggested that diffusion alone was insufficient for normal oxygen delivery in mitral valves ...[more]

PMID: 28003526

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Project description:BackgroundThe durability of transcatheter aortic valves (TAVs) remains their greatest disadvantage, given that fixed tissue leaflets are not immune to structural degeneration from calcification and thrombosis. Therefore, a second intervention is necessary, especially given that TAV in low-risk patients has shown noninferior outcomes compared with surgery. This study aimed to assess the hemodynamic and turbulent properties of the flow downstream with different TAV-in-TAV configurations, to offer basic hemodynamic guidance for future interventions when currently implanted valves structurally degrade.MethodsSix TAV-in-TAV configurations were chosen: 23 mm Evolut-in-26 mm Evolut, 23 mm Evolut-in-23 mm SAPIEN 3, 26 mm Evolut-in-26 mm Evolut, 26 mm Evolut-in-23 mm SAPIEN 3, 23 mm SAPIEN3-in-26 mm Evolut, and 23 mm SAPIEN3-in-23 mm SAPIEN 3. Their hemodynamic performance was assessed in a pulse duplicator for 100 cycles. High-speed imaging and particle image velocimetry were performed to assess turbulence. Effective orifice area (EOA), pinwheeling index (PI), and Reynolds shear stress (RSS) were evaluated.ResultsThe largest mean EOA was obtained with 23 mm SAPIEN-in-26 mm Evolut (2.07 ± 0.06 cm2), and the smallest was obtained with 23 mm Evolut-in-23 mm SAPIEN (1.50 ± 0.04 cm2) (P < .001). The highest mean PI was obtained with SAPIEN-in-SAPIEN (26.5 ± 2.00%), and the lowest was obtained with 26 mm Evolut-in-26 mm Evolut (7.5 ± 1.6%) (P < .01). At peak systole, the least detrimental RSS range was obtained with 23 mm Evolut-in-26 mm Evolut (up to ∼340 Pa), and the most detrimental RSS range was obtained with 23 mm Evolut-in-SAPIEN (∼900 Pa) (P < .01).ConclusionsThis study shows that best hemodynamic parameters are TAV-specific (implanted and to be implanted). In addition, it shows that RSS levels, which are indicative of turbulence levels and associated with blood damage, are 2- to 3-fold higher after TAV-in-TAV.

Dataset Information

Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves.

Publications

Differential cell-matrix responses in hypoxia-stimulated aortic versus mitral valves.

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