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Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold.

ABSTRACT: Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols that preserve BM components are necessary to advance the field. This study aims to characterize laminin isoforms expressed in healthy human aortic valves and establish a small animal decellularized aortic valve scaffold for future studies of the BM in tissue engineering. Laminin isoforms were assessed by immunohistochemistry with antibodies specific for individual ?, ?, and ? chains. The results indicated that LN-411, LN-421, LN-511, and LN-521 are expressed in human aortic valves (n?=?3), forming a continuous monolayer in the endothelial BM, whereas sparsely found in the interstitium. Similar results were seen in rat aortic valves (n?=?3). Retention of laminin and other BM components, concomitantly with effective removal of cells and residual DNA, was achieved through 3?h exposure to 1% sodium dodecyl sulfate and 30?min exposure to 1% Triton X-100, followed by nuclease processing in rat aortic valves (n?=?3). Our results provide crucial data on the microenvironment of valvular cells relevant for research in both tissue engineering and heart valve biology. We also describe a decellularized rat aortic valve scaffold useful for mechanistic studies on the role of the BM in heart valve regeneration.

SUBMITTER: Granath C

PROVIDER: S-EPMC7757704 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold.

Granath Carl C Noren Hunter H Björck Hanna H Simon Nancy N Olesen Kim K Rodin Sergey S Grinnemo Karl-Henrik KH Österholm Cecilia C

BioResearch open access 20201207 1

Aortic valve stenosis is one of the most common cardiovascular diseases in western countries and can only be treated by replacement with a prosthetic valve. Tissue engineering is an emerging and promising treatment option, but in-depth knowledge about the microstructure of native heart valves is lacking, making the development of tissue-engineered heart valves challenging. Specifically, the basement membrane (BM) of heart valves remains incompletely characterized, and decellularization protocols ...[more]

PMID: 33376633

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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

Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold.

Publications

Characterization of Laminins in Healthy Human Aortic Valves and a Modified Decellularized Rat Scaffold.

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