Interstitial cells in calcified aortic valves have reduced differentiation potential and stem cell-like properties

Sci Rep. 2019 Sep 10;9(1):12934. doi: 10.1038/s41598-019-49016-0.


Valve interstitial cells (VICs) are crucial in the development of calcific aortic valve disease. The purpose of the present investigation was to compare the phenotype, differentiation potential and stem cell-like properties of cells from calcified and healthy aortic valves. VICs were isolated from human healthy and calcified aortic valves. Calcification was induced with osteogenic medium. Unlike VICs from healthy valves, VICs from calcified valves cultured without osteogenic medium stained positively for calcium deposits with Alizarin Red confirming their calcific phenotype. Stimulation of VICs from calcified valves with osteogenic medium increased calcification (p = 0.02), but not significantly different from healthy VICs. When stimulated with myofibroblastic medium, VICs from calcified valves had lower expression of myofibroblastic markers, measured by flow cytometry and RT-qPCR, compared to healthy VICs. Contraction of collagen gel (a measure of myofibroblastic activity) was attenuated in cells from calcified valves (p = 0.04). Moreover, VICs from calcified valves, unlike cells from healthy valves had lower potential to differentiate into adipogenic pathway and lower expression of stem cell-associated markers CD106 (p = 0.04) and aldehyde dehydrogenase (p = 0.04). In conclusion, VICs from calcified aortic have reduced multipotency compared to cells from healthy valves, which should be considered when investigating possible medical treatments of aortic valve calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aortic Valve / metabolism
  • Aortic Valve / pathology*
  • Aortic Valve Stenosis / genetics
  • Aortic Valve Stenosis / metabolism
  • Aortic Valve Stenosis / pathology*
  • Bicuspid Aortic Valve Disease
  • Biomarkers / analysis*
  • Calcinosis / genetics
  • Calcinosis / metabolism
  • Calcinosis / pathology*
  • Cell Differentiation*
  • Cells, Cultured
  • Female
  • Gene Expression Profiling
  • Heart Defects, Congenital / genetics
  • Heart Defects, Congenital / metabolism
  • Heart Defects, Congenital / pathology*
  • Heart Valve Diseases / genetics
  • Heart Valve Diseases / metabolism
  • Heart Valve Diseases / pathology*
  • Humans
  • Interstitial Cells of Cajal / metabolism
  • Interstitial Cells of Cajal / pathology*
  • Male
  • Myofibroblasts / cytology
  • Myofibroblasts / metabolism
  • Osteogenesis*
  • Stem Cells / metabolism
  • Stem Cells / pathology*


  • Biomarkers

Supplementary concepts

  • Aortic Valve, Calcification of