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Rho GTPases in the regulation of pulmonary vascular barrier function

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Abstract

Pulmonary endothelial permeability is an important determinant of vascular adaptation to changes in oxygen tension, blood pressure, levels of growth factors or inflammatory cytokines. The Ras homologous (Rho) family of guanosine triphosphate phosphatases (Rho GTPases), key regulators of the actin cytoskeleton, regulate endothelial barrier function in response to a variety of environmental factors and signalling agents via the reorganization of the actin cytoskeleton, changes in receptor trafficking or the phosphorylation of junctional proteins. This review provides a brief summary of recent knowledge on Rho-GTPase-mediated effects on pulmonary endothelial barrier function and focuses in particular on their role in pulmonary vascular disorders, including pulmonary hypertension, chronic obstructive pulmonary disease, acute lung injury and acute respiratory distress syndrome.

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Abbreviations

ADMA:

Asymmetric dimethylarginine

AJ:

Adherens junction

ALI:

Acute lung injury

ARDS:

Acute respiratory distress syndrome

Cx:

Connexin

DDAH:

Dimethylarginine dimethylhydrolase

eNOS:

Endothelial nitric oxide synthase

ET-1:

Endothelin-1

GAPs:

GTPase-activating proteins

GEFs:

Guanine nucleotide exchange factors

GDIs:

Guanine nucleotide dissociation inhibitors

GDP:

Guanosine diphosphate

GJ:

Gap junction

GTP:

Guanosine triphosphate

GTPase:

GTP phosphatase

HGF:

Hepatocyte growth factor

HIF1α:

Hypoxia inducible factor 1 alpha

HPAECs:

Human pulmonary artery endothelial cells

LPS:

Lipopolysaccharide

MLC20 :

Myosin light chain 20

MLCK:

Myosin light chain kinase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NO:

Nitric oxide

OxPAPC:

Oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphatidylcholine

PAECs:

Pulmonary artery endothelial cells

PAH:

Pulmonary arterial hypertension

PAK:

p21-activated protein kinase

PH:

Pulmonary hypertension

PKC:

Protein kinase C

PKG:

Protein kinase G

Rho:

Ras homologous

ROCK:

Rho kinase

ROS:

Reactive oxygen species

S1P:

Sphingosine-1 phosphate

TJ:

Tight junction

TNF-α:

Tumour necrosis factor alpha

VASP:

Vasodilator-stimulated phosphoprotein

VE-cadherin:

Vascular endothelial cadherin

VEGF:

Vascular endothelial growth factor

ZO-1:

Zonula occludens protein 1

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Authors and Affiliations

  1. Centre for Pharmacology & Therapeutics, Imperial College London, London, UK

    Lucie Duluc & Beata Wojciak-Stothard

  2. Department of Experimental Medicine and Toxicology, Imperial College London, Office 535, Laboratory 504, 5th floor ICTEM Building, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    Beata Wojciak-Stothard

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  1. Lucie Duluc
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  2. Beata Wojciak-Stothard
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Correspondence to Beata Wojciak-Stothard.

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Duluc, L., Wojciak-Stothard, B. Rho GTPases in the regulation of pulmonary vascular barrier function. Cell Tissue Res 355, 675–685 (2014). https://doi.org/10.1007/s00441-014-1805-0

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