NFATc1 mediates vascular endothelial growth factor-induced proliferation of human pulmonary valve endothelial cells

Ehrin N. Johnson, You Mie Lee, Tara L. Sander, Elena Rabkin, Frederick J. Schoen, Sunjay Kaushal, Joyce Bischoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Mice deficient for the transcription factor NFATc1 fail to form pulmonary and aortic valves, a defect reminiscent of some types of congenital human heart disease. We examined the mechanisms by which NFATc1 is activated and translocated to the nucleus in human pulmonary valve endothelial cells to gain a better understanding of its potential role(s) in post-natal valvular repair as well as valve development. Herein we demonstrate that activation of NFATc1 in human pulmonary valve endothelial cells is specific to vascular endothelial growth factor (VEGF) signaling through VEGF receptor 2. VEGF-induced NFATc1 nuclear translocation was inhibited by either cyclosporin A or a calcineurin-specific peptide inhibitor; these findings suggest that VEGF stimulates NFATc1 nuclear import in human pulmonary valve endothelial cells by a calcineurin-dependent mechanism. Importantly, both cyclosporin A and the calcineurin-specific peptide inhibitor reduced VEGF-induced human pulmonary valve endothelial cell proliferation, indicating a functional role for NFATc1 in endothelial growth. In contrast, VEGF-induced proliferation of human dermal microvascular and human umbilical vein endothelial cells was not sensitive to cyclosporin A. Finally, NFATc1 was detected in the endothelium of human pulmonary valve leaflets by immunohistochemistry. These results suggest VEGF-induced NFATcl activation may be an important mechanism in cardiac valve maintenance and function by enhancing endothelial proliferation.

Original languageEnglish (US)
Pages (from-to)1686-1692
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number3
DOIs
StatePublished - Jan 17 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'NFATc1 mediates vascular endothelial growth factor-induced proliferation of human pulmonary valve endothelial cells'. Together they form a unique fingerprint.

Cite this