Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during Flow-Dependent vascular remodeling

Jun Yu, Yuanyuan Zhang, Xinbo Zhang, R. Daniel Rudic, Philip M. Bauer, Dario C. Altieri, William C. Sessa

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS) in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/-)) is associated with activation of the platelet derived growth factor (PDGF) signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/-) mice. Moreover, nitric oxide (NO) negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

Original languageEnglish (US)
Article numbere31495
JournalPloS one
Volume7
Issue number2
DOIs
StatePublished - Feb 15 2012

ASJC Scopus subject areas

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

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