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Basic fibroblast growth factor inhibits aortic valvular interstitial cells calcification via Notch1 pathway
  1. Yuan Gao1,
  2. Ning Li1,2,
  3. Qing Xue1,
  4. Xinli Fan1,
  5. Xiaohong Liu1,
  6. Lin Han1
  1. 1 Department of Cardiothoracic Surgery, Changhai Hospital, Shanghai, China
  2. 2 Department of Cardiothoracic Surgery, Naval Medical Center of PLA, Shanghai, People's Republic of China
  1. Correspondence to Dr Lin Han, Changhai Hospital, Shanghai, China; 2206100117{at}


Calcific aortic valve disease (CAVD) is an active pathological process mediated by abnormal activation and transdifferentiation of valvular interstitial cells (VICs). The present study aims to investigate the function and underlying mechanism of the basic fibroblast growth factor (BFGF) on osteogenic differentiation of VICs. Porcine VICs cultured with osteogenic induction medium are supplemented with or without BFGF. Morphology of VICs is identified by fluorescein isothiocyanate-labeled phalloidin, the cell viability is assessed by the cell counting kit-8 method, and protein and mRNA expression level of osteogenic differentiation markers, including Runx2, osteopontin, and Sp7, are verified by western blot analysis and quantitative real-time PCR, respectively. RNA sequencing is used to identify changes in gene profiles. Alizarin Red S staining is used to measure calcium deposition. The results demonstrate that the content of calcium deposition and the expression level of osteogenic markers are downregulated by supplementing BFGF. Notch1 signaling pathway is extracted as a candidate target after bioinformatics analysis by RNA sequencing. The transfection of si-Notch1 abolishes the calcification inhibitory effect of BFGF. Taken together, our findings shed the light on the mechanism and potential therapeutics of BFGF for CAVD.

  • medicine
  • biomedical research
  • heart
  • phenotype

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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  • YG and NL contributed equally.

  • Contributors HL and LX conceived the ideas. GY and LN designed the experiments. GY performed the experiments. LN analyzed the data. XQ and FX provided critical materials. LN and GY wrote the manuscript. HL and LX supervised the study. All the authors have read and approved the final version for publication. HL was responsible for the overall content as the guarantor.

  • Funding This work was supported by National Natural Science Foundation of China (grant no. 82100383, 81770383); National Key Research and Development Program of China (grant no. 2016YFC1100900).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.