Aortic Valve Endothelial Cells Undergo Transforming Growth Factor-Beta-Mediated and Non-Transforming Growth Factor-Beta-Mediated Transdifferentiation in Vitro

Am J Pathol. 2001 Oct;159(4):1335-43. doi: 10.1016/s0002-9440(10)62520-5.


Cardiac valves arise from endocardial cushions, specialized regions of the developing heart that are formed by an endothelial-to-mesenchymal cell transdifferentiation. Whether and to what extent this transdifferentiation is retained in mature heart valves is unknown. Herein we show that endothelial cells from mature valves can transdifferentiate to a mesenchymal phenotype. Using induction of alpha-smooth muscle actin (alpha-SMA), an established marker for this process, two distinct pathways of transdifferentiation were identified in clonally derived endothelial cell populations isolated from ovine aortic valve leaflets. alpha-SMA expression was induced by culturing clonal endothelial cells in medium containing either transforming growth factor-beta or low levels of serum and no basic fibroblast growth factor. Cells induced to express alpha-SMA exhibited markedly increased migration in response to platelet-derived growth factor-BB, consistent with a mesenchymal phenotype. A population of the differentiated cells co-expressed CD31, an endothelial marker, along with alpha-SMA, as seen by double-label immunofluorescence. Similarly, this co-expression of endothelial markers and alpha-SMA was detected in a subpopulation of cells in frozen sections of aortic valves, suggesting the transdifferentiation may occur in vivo. Hence, the clonal populations of valvular endothelial cells described here provide a powerful in vitro model for dissecting molecular events that regulate valvular endothelium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aortic Valve / pathology*
  • Aortic Valve / physiopathology
  • Cell Differentiation / physiology
  • Cell Movement / physiology
  • Cells, Cultured
  • Clone Cells
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology
  • Humans
  • Sheep
  • Transforming Growth Factor beta / physiology*


  • Transforming Growth Factor beta