Cellular Mechanisms of Aortic Valve Calcification

Жидулева, Е. В.; Irtyuga, Olga; Шишкова, А. А.; Игнатьева, Е. В.; Kostina, Aleksandra; Levchuk, Ksenia; Головкин, А. С.; Rylov, A. Yu.; Kostareva, Anna; Моисеева, О. М.; Malashicheva, Anna; Гордеев, М. Л.

doi:10.1007/s10517-018-3992-2

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…It is known that OPN intensively stains calcified regions in sclerotic aortic valves [ 57 , 58 ] but the functional role of OPN in CAVD is still controversial. OPN may bind to apatite crystals and is considered as a potential mineralization inhibitor [ 59 ] though at the same time OPN expression increases with the progression and calcification in human aortic valve tissue [ 60 ] suggesting a pro-degenerative role.…”

Section: Discussionmentioning

confidence: 99%

Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow

et al. 2021

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Calcific aortic valve disease is the most common valvular heart disease in industrialized countries. Pulsatile pressure, sheer and bending stress promote initiation and progression of aortic valve degeneration. The aim of this work is to establish an ex vivo model to study the therein involved processes. Ovine aortic roots bearing aortic valve leaflets were cultivated in an elaborated bioreactor system with pulsatile flow, physiological temperature, and controlled pressure and pH values. Standard and pro-degenerative treatment were studied regarding the impact on morphology, calcification, and gene expression. In particular, differentiation, matrix remodeling, and degeneration were also compared to a static cultivation model. Bioreactor cultivation led to shrinking and thickening of the valve leaflets compared to native leaflets while gross morphology and the presence of valvular interstitial cells were preserved. Degenerative conditions induced considerable leaflet calcification. In comparison to static cultivation, collagen gene expression was stable under bioreactor cultivation, whereas expression of hypoxia-related markers was increased. Osteopontin gene expression was differentially altered compared to protein expression, indicating an enhanced protein turnover. The present ex vivo model is an adequate and effective system to analyze aortic valve degeneration under controlled physiological conditions without the need of additional growth factors.

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Section: Discussionmentioning

confidence: 99%

Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow

et al. 2021

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“…To date, there have been no effective medications to prevent valvular calcification. Statins and angiotensin‐converting enzyme inhibitors have been highly hopeful, but many of their large clinical trials have confirmed that neither treatment can effectively slow the progression of this disease (Zhiduleva et al, ). Currently, a reasonable daily diet or health care food supplements may be the most effective way to suppress CHVD progress.…”

Section: Introductionmentioning

confidence: 99%

Nobiletin exhibits potent inhibition on tumor necrosis factor alpha‐induced calcification of human aortic valve interstitial cells via targeting ABCG2 and AKR1B1

Huang

Zhou

et al. 2019

Phytotherapy Research

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Inflammation is considered to be one of the initial critical factors in the occurrence of calcific heart valve disease. This study was to prove Nobiletin (NBT) inhibits inflammation‐caused calcification of human valve interstitial cells (hVICs) and to elucidate the involved molecular mechanisms. Tumor necrosis factor‐alpha (TNF‐α)‐induced hVICs were treated with or without NBT. Cell growth and calcification of hVICs were assessed. RNA sequencing was utilized to investigate the gene expression changes. Molecular target prediction and docking assay were further performed. NBT interfered with hVIC growth under TNF‐α condition in a dose‐dependent manner also presented a gradual decrease of positive Alizarin Red S staining, down‐regulation of BMP2, and RUNX2 gene expression. Based on the global gene expression cluster, control and TNF‐α plus NBT group showed a high similarity versus TNF‐α only group. After Venn interaction of differential expression genes (DEGs), 2,236 common DEGs were identified to display different biological functions and signaling pathways. ABCG2 and AKR1B1 were further selected as prediction targets of NBT involved in RELA, TNF, BMP2, RUNX2, etc. interactions in mediating hVIC calcification. The results show that NBT is a natural product to prevent the occurrence of heart valve calcification.

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“…Currently, there are no effective preventive measures to treat CHVD, given that the underlying mechanisms of the disease are not very well understood. Statins and ACE inhibitors have been highly hopeful, but many of their large clinical trials have confirmed that neither treatment can effectively slow the progression of this disease ( Zhiduleva et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Anthraquinone Emodin Inhibits Tumor Necrosis Factor Alpha-Induced Calcification of Human Aortic Valve Interstitial Cells via the NF-κB Pathway

Zhou

Huang

et al. 2018

Front. Pharmacol.

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Exploring effective therapies for delaying calcific heart valve disease (CHVD) is the focus of current cardiovascular clinical and scientific research. In this study, human aortic valve interstitial cells (hVICs) were isolated from patients with CHVD. After expansion, cultured hVICs were induced with the tumor necrosis factor-alpha (TNF-α) with or without anthraquinone emodin (EMD) treatments. Cytotoxicity and flow cytometric analysis were used to assess cell growth, while Alizarin Red S staining was used to detect hVICs calcification. Furthermore, RNA-sequencing analysis was utilized to investigate changes in mRNA profiles of cells cultured in TNF-α conditioned medium with or without EMD. Western blotting and qRT-PCR analyses were used for the verification of key selected genes. Our results indicated that EMD had limited influence on hVIC morphology, whereas in a dose-dependent fashion, EMD interfered with hVIC growth under TNF-α conditioned cell culture. Additionally, hVICs treated with TNF-α plus EMD, presented a gradual decrease of positive Alizarin Red S staining, when compared with cells treated with TNF-α only. Notably, cells treated with TNF-α plus EMD showed 1874 differential expression genes (DEGs), among them, 1131 were upregulated and 743 were downregulated. These DEGs displayed an enrichment of biological functions and signaling pathways, among them, BMP2, RELA, TNF, and TRAF1, were found to be significantly suppressed by EMD and selected given their role in mediating hVIC calcification. In conclusion, our study shows that EMD inhibits TNF-α-induced calcification and phenotypical transformation of hVICs via the NF-κB signaling pathway, thereby preventing calcification events stimulated during acute inflammatory responses.

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Cellular Mechanisms of Aortic Valve Calcification

Cited by 10 publications

References 13 publications

Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow

Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow

Nobiletin exhibits potent inhibition on tumor necrosis factor alpha‐induced calcification of human aortic valve interstitial cells via targeting ABCG2 and AKR1B1

Anthraquinone Emodin Inhibits Tumor Necrosis Factor Alpha-Induced Calcification of Human Aortic Valve Interstitial Cells via the NF-κB Pathway

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