Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

PloS One
Jun YuW C Sessa

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.

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Citations

Jun 21, 2014·Pharmacological Reports : PR·Magdalena Jasińska-Stroschein, Daria Orszulak-Michalak
Sep 11, 2013·International Journal of Cardiology·Richmond W JeremyBrett D Hambly
Dec 3, 2014·Journal of Vascular Surgery·Daniel J WongAlan Dardik
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Jun 14, 2012·Circulation Research·Francesco PaneniFrancesco Cosentino
Jun 14, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Begoña LavinCarlos Zaragoza
Nov 9, 2018·Frontiers in Cardiovascular Medicine·Manna LiJian Xu
Dec 17, 2020·Frontiers in Immunology·Vitaly SorokinCatherine M Shanahan
Jul 25, 2021·International Journal of Molecular Sciences·Nerea Méndez-BarberoLuis Miguel Blanco-Colio

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