Angiogenesis

, Volume 6, Issue 1, pp 55–64

Caldesmon-dependent switching between capillary endothelial cell growth and apoptosis through modulation of cell shape and contractility

  • Yasushi Numaguchi
  • Sui Huang
  • Thomas R. Polte
  • Gabriel S. Eichler
  • Ning Wang
  • Donald E. Ingber
Article

DOI: 10.1023/A:1025821517679

Cite this article as:
Numaguchi, Y., Huang, S., Polte, T.R. et al. Angiogenesis (2003) 6: 55. doi:10.1023/A:1025821517679
  • 82 Downloads

Abstract

Caldesmon (CaD), a protein component of the actomyosin filament apparatus, modulates cell shape and cytoskeletal structure when overexpressed. When capillary endothelial cells were infected with an adenoviral vector encoding GFP-CaD under Tet-Off control, progressive inhibition of contractility, loss of actin stress fibers, disassembly of focal adhesions, and cell retraction resulted. This was accompanied by a cell shape (rounding)-dependent increase in apoptosis and concomitant inhibition of cell cycle progression. Cell growth also was inhibited in low expressor cells in which cell tension was suppressed independently of significant changes in cell shape, cytoskeletal structure, or focal adhesions. Thus, changes in both cytoskeletal structure and contractility appear to be central to the mechanism by which extracellular matrix-dependent changes in capillary cell shape influence growth and apoptosis during angiogenesis, and hence the cytoskeleton may represent a potential target for anti-angiogenesis therapy.

cell cyclecytoskeletonextracellular matrixmechanical forcemicrofilamenttension

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Yasushi Numaguchi
    • 1
  • Sui Huang
    • 1
  • Thomas R. Polte
    • 1
  • Gabriel S. Eichler
    • 1
  • Ning Wang
    • 2
  • Donald E. Ingber
    • 3
  1. 1.Vascular Biology Program, Departments of Pathology and SurgeryChildren’s Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Physiology ProgramHarvard School of Public HealthBostonUSA
  3. 3.Vascular Biology Program, Departments of Pathology and SurgeryChildren’s Hospital and Harvard Medical SchoolBostonUSA