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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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

Fingerprint

platelet-derived growth factor
Nitric Oxide Synthase Type III
Platelet-Derived Growth Factor
nitric oxide synthase
endothelium
blood vessels
Nitric Oxide Synthase
Nitric Oxide
mice
Vascular Smooth Muscle
Knockout Mice
smooth muscle
myocytes
blood flow
shear stress
Smooth Muscle Myocytes
nitric oxide
Muscle
Vascular Remodeling
Shear stress

ASJC Scopus subject areas

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

Cite this

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during Flow-Dependent vascular remodeling. / Yu, Jun; Zhang, Yuanyuan; Zhang, Xinbo; Rudic, Radu Daniel; Bauer, Philip M.; Altieri, Dario C.; Sessa, William C.

In: PloS one, Vol. 7, No. 2, e31495, 15.02.2012.

Research output: Contribution to journalArticle

Yu, Jun ; Zhang, Yuanyuan ; Zhang, Xinbo ; Rudic, Radu Daniel ; Bauer, Philip M. ; Altieri, Dario C. ; Sessa, William C. / Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during Flow-Dependent vascular remodeling. In: PloS one. 2012 ; Vol. 7, No. 2.
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