Calpain-2 regulation of VEGF-mediated angiogenesis

Yunchao Su, Zhaoqiang Cui, Zhaozhong Li, Edward R. Block

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Angiogenesis is a complex process involving endothelial cell migration, proliferation, and differentiation as well as tube formation. These processes are stimulated by a variety of growth factors such as vascular endothelial growth factor (VEGF). VEGF-induced cytoskeletal reorganization plays a crucial role in the angiogenic processes. In the present study, we evaluated the role of calpain in VEGF-induced angiogenesis in vitro and in vivo. Human pulmonary microvascular endothelial cells (PMEC) were incubated with VEGF (10-60 ng/ml) for 2-24 h, after which we measured calpain activities, protein contents of the calpain subunits and of calpastatin, endothelial monolayer wound repair, tube formation, and actin cytoskeleton changes. Incubation of PMEC with VEGF resulted in dose- and time-dependent increases in calpain activity and protein content of calpain-2. VEGF did not change the protein contents of calpain-1 and the small subunit or of calpastatin. Incubation of PMEC with a VEGF receptor blocker prevented the VEGF-induced increase in calpain activity. Inhibition of calpain activity by siRNA directed against calpain-2 and by overexpression of calpastatin prevented VEGF-induced increases in actin stress fibers in endothelial cells and angiogenesis. Overexpression of calpastatin also inhibits vessel formation in subcutaneous (s.c.) matrigel plugs in mice. These results indicate that calpain mediates VEGF-induced angiogenic effects by modulating actin cytoskeletal organization.

Original languageEnglish (US)
Pages (from-to)1443-1451
Number of pages9
JournalFASEB Journal
Volume20
Issue number9
DOIs
StatePublished - Jul 1 2006
Externally publishedYes

Fingerprint

calpain
Calpain
vascular endothelial growth factors
angiogenesis
Vascular Endothelial Growth Factor A
Endothelial cells
calpastatin
endothelial cells
Endothelial Cells
Actins
lungs
protein content
Lung
actin
vascular endothelial growth factor receptors
Stress Fibers
Vascular Endothelial Growth Factor Receptor
Proteins
small interfering RNA
microfilaments

Keywords

  • Actin
  • Calpains
  • Calpastatin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Calpain-2 regulation of VEGF-mediated angiogenesis. / Su, Yunchao; Cui, Zhaoqiang; Li, Zhaozhong; Block, Edward R.

In: FASEB Journal, Vol. 20, No. 9, 01.07.2006, p. 1443-1451.

Research output: Contribution to journalArticle

Su, Y, Cui, Z, Li, Z & Block, ER 2006, 'Calpain-2 regulation of VEGF-mediated angiogenesis', FASEB Journal, vol. 20, no. 9, pp. 1443-1451. https://doi.org/10.1096/fj.05-5354com
Su, Yunchao ; Cui, Zhaoqiang ; Li, Zhaozhong ; Block, Edward R. / Calpain-2 regulation of VEGF-mediated angiogenesis. In: FASEB Journal. 2006 ; Vol. 20, No. 9. pp. 1443-1451.
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