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Redox regulation of vascular remodeling

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Abstract

Vascular remodeling is a dynamic process of structural and functional changes in response to biochemical and biomechanical signals in a complex in vivo milieu. While inherently adaptive, dysregulation leads to maladaptive remodeling. Reactive oxygen species participate in homeostatic cell signaling in tightly regulated- and compartmentalized cellular circuits. It is well established that perturbations in oxidation–reduction (redox) homeostasis can lead to a state of oxidative-, and more recently, reductive stress. We provide an overview of the redox signaling in the vasculature and review the role of oxidative- and reductive stress in maladaptive vascular remodeling. Particular emphasis has been placed on essential processes that determine phenotype modulation, migration and fate of the main cell types in the vessel wall. Recent advances in systems biology and the translational opportunities they may provide to specifically target the redox pathways driving pathological vascular remodeling are discussed.

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Abbreviations

AngII:

Angiotensin II

AP1:

Activator protein 1

AT1R:

Angiotensin II type 1 receptor

BH4 :

Tetrahydrobiopterin

Cys:

Cysteine

Cys-SH:

Cysteinyl thiolates

Cys-S-SH:

Cysteinyl persulfide

EC:

Endothelial cell

ECM:

Extracellular matrix

eNOS:

Endothelial nitric oxide synthase

FAK:

Focal adhesion kinase

GCHI:

Guanosine triphosphate cyclohydrolase I

GSS:

S-Glutathiolation

GTP:

Guanosine triphosphate

Hic5:

H2O2-inducible clone-5

HSP27:

Heat shock protein 27

Nox:

NADPH oxidase

Keap1:

Kelch-like ECH-associated protein 1

LMW-PTP:

Low molecular weight protein tyrosine phosphatase

MAPKAPK2:

Mitogen-activated protein kinase-activated protein kinase 2

MEF2:

Myocyte-enhanced factor 2

MLC:

Myosin light chain

MLCP:

Myosin light chain phosphatase

MRTF-A:

Myocardin-related transcription factor A

NF-κB:

Nuclear factor κB

Nrf2:

Nuclear factor erythroid 2-related factor 2

p38 MAPK:

p38 mitogen-activated protein kinase

PDGFβ:

Platelet-derived growth factor β

PDGFR:

Platelet-derived growth factor receptor

PI3K:

Phosphoinositol 3-kinase

PIP3:

Phosphatidylinositol 3,4,5 trisphosphate

PKCζ:

Protein kinase Cζ

Poldip2:

Polymerase [DNA-directed] delta-interacting protein 2

PTEN:

Phosphatase and tensin homolog

ROCK:

Rho-kinase

ROS:

Reactive oxygen species

SMC:

Smooth muscle cell

SOD:

Superoxide dismutase

SRF:

Serum response factor

SSH1L:

Slingshot1L phosphatase,

TAT3:

Signal transducer and activator of transcription 3

TGFβ:

Transforming growth factor β

TXNIP:

Thioredoxin-interacting protein

VEGF:

Vascular endothelial growth factor

VEGF-R:

Vascular endothelial growth factor receptor

WSS:

Wall shear stress

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Acknowledgments

KKG is supported by a Columbia University Research Grant and Lucy Falkiner Fellowship from Sydney Medical School Foundation. ZAA is supported by NIH Grant R00HL109256.

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Authors and Affiliations

  1. Division of Cardiology, Center for Interventional Vascular Therapy, New York Presbyterian Hospital and Columbia University, New York, NY, USA

    Keyvan Karimi Galougahi & Ziad A. Ali

  2. Sydney Medical School Foundation, University of Sydney, Sydney, Australia

    Keyvan Karimi Galougahi

  3. Division of Cardiology, Stanford University, Stanford, CA, USA

    Euan A. Ashley

  4. Cardiovascular Research Foundation, New York, NY, USA

    Ziad A. Ali

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  1. Keyvan Karimi Galougahi
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Correspondence to Keyvan Karimi Galougahi.

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Karimi Galougahi, K., Ashley, E.A. & Ali, Z.A. Redox regulation of vascular remodeling. Cell. Mol. Life Sci. 73, 349–363 (2016). https://doi.org/10.1007/s00018-015-2068-y

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