scholarly journals High fructose induced osteogenic differentiation of human valve interstitial cells via activating PI3K/AKT/mitochondria signaling

2021 ◽  
Author(s):  
Hsiao-Huang Chang ◽  
I-Chun Lin ◽  
Chih-Wei Wu ◽  
Chun-Ying Hung ◽  
Wen-Chung Liu ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Fan Zhang ◽  
Naixuan Cheng ◽  
Yingchun Han ◽  
Congcong Zhang ◽  
Haibo Zhang

Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene RUNX2, and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene FZD4 and CTNNB1. In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs via the Wnt/β-Catenin pathway, which may further provide a new therapeutic target for CAVD.


2018 ◽  
Vol 9 ◽  
Author(s):  
Maria Bogdanova ◽  
Aleksandra Kostina ◽  
Katarina Zihlavnikova Enayati ◽  
Arsenii Zabirnyk ◽  
Anna Malashicheva ◽  
...  

2020 ◽  
Vol 159 (5) ◽  
pp. 1742-1753.e7 ◽  
Author(s):  
Yongjun Wang ◽  
Xiaoxiong Xiao ◽  
Tingwen Zhou ◽  
Dong Han ◽  
Nianguo Dong

2021 ◽  
Author(s):  
Chunli wang ◽  
Yi Xia ◽  
Linghang Qu ◽  
Yanju Liu ◽  
Xianqiong Liu ◽  
...  

Cardamonin (CDM) is a natural chalcone with strong anti-inflammatory properties. Inflammation-induced osteogenic changes in valve interstitial cells (VICs) play crucial roles in the development of calcific aortic valve disease (CAVD),...


2021 ◽  
Vol 10 (3) ◽  
pp. 44-55
Author(s):  
D. S. Semenova ◽  
A. M. Kiselev ◽  
A. B. Malashicheva

Aim. Calcified aortic valve stenosis is the third leading cause of cardiovascular disease. The mechanisms underlying this process remain unclear, however, it is known that they are largely similar to the formation of bone tissue during embryonic development, as well as in the postnatal period during regeneration. There is evidence for the             involvement of Zinc Finger and BTB Domain Containing 16 (ZBTB16) in skeletal development. At the same time, a number of studies carried out on different types of cell cultures indicate a contradictory and ambiguous effect of ZBTB16 on RUNX2 expression. Thus, the aim of this study was to investigate the dynamic variability of ZBTB16 expression, as well as its role in aortic valve calcification.Methods. The study used different types of mesenchymal cells cultures - aortic valve interstitial cells, umbilical cord mesenchymal stem cells, ligament stem cells and dental pulp stem cells. Changes in ZBTB16 and RUNX2 expression levels                under the influence of osteogenic stimuli, as well as during exogenous activation of ZBTB16, were analyzed using real-time PCR. Expression levels of some osteogenic markers - BMP2,4, COL1A1, IBSP, DLX2, PDK4 - were analyzed in the interstitial cells of the aortic valve.Results. The results of the study indicate that a significant increase in the expression of ZBTB16 is observed during the induction of osteogenic differentiation of various cell cultures - interstitial cells of the aortic valve, mesenchymal stem cells of           the umbilical cord, stem cells of the ligaments and dental pulp. Apparently, the processes of osteogenic differentiation of aortic valve interstitial cells, in the presence of dexamethasone in cultivation medium, are provided through RUNX2-dependent signaling for the further activation of osteogenic markers.Conclusion. The study of modulation of cellular signals by ZBTB16, when activating or suppressing the work of a transcriptional factor, in the future may bring us closer to the ability to enhance the regenerative abilities of bone tissue cells or, conversely, prevent calcification of the aortic valve tissues.


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