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Today’s and tomorrow’s imaging and circulating biomarkers for pulmonary arterial hypertension

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Abstract

The pathobiology of pulmonary arterial hypertension (PAH) involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis, leading to an increase in pulmonary vascular resistance, right heart failure and death. Its etiology may be idiopathic, but PAH is also frequently associated with underlying conditions such as connective tissue diseases. During the past decade, more than welcome novel therapies have been developed and are in development, including those increasingly targeting the remodeling process. These therapeutic options modestly increase the patients’ long-term survival, now approaching 60% at 5 years. However, non-invasive tools for confirming PAH diagnosis, and assessing disease severity and response to therapy, are tragically lacking and would help to select the best treatment. After exclusion of other causes of pulmonary hypertension, a final diagnosis still relies on right heart catheterization, an invasive technique which cannot be repeated as often as an optimal follow-up might require. Similarly, other techniques and biomarkers used for assessing disease severity and response to treatment generally lack specificity and have significant limitations. In this review, imaging as well as current and future circulating biomarkers for diagnosis, prognosis, and follow-up are discussed.

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Abbreviations

5-HT:

Serotonin or 5-hydroxytryptamine

BMP:

Bone morphogenetic protein

BMPRII:

BMP receptor 2

BNP:

Brain natriuretic peptide

cGMP:

Cyclic guanosine 3′5′-monophosphate

CT:

Computed tomography

CTEPH:

Chronic thromboembolic pulmonary hypertension

DCE:

Delayed contrast enhancement

Echo:

Echocardiography

EGF:

Epidermal growth factor

eNOS:

Endothelial nitric oxide synthase

ET-1/3:

Endothelin 1 or 3

FC:

Functional class

HDL-C:

High-density lipoprotein cholesterol

IL-6:

Interleukin 6

iPAH:

Idiopathic PAH

LIGHT:

Lymphotoxin-like inducible protein

LV:

Left ventricle

miR-X:

MicroRNA-X

miRNA:

Micro RNA

MP:

Microparticles

MRI:

Magnetic resonance imaging

NFAT:

Nuclear factor of activated T cells

NO:

Nitric oxide

NT-proBNP:

N-terminal pro-brain natriuretic peptide

OPN:

Osteopontin

PA:

Pulmonary arteries

PAAT:

Pulmonary artery acceleration time

PAH:

Pulmonary arterial hypertension

PAP:

Pulmonary arterial pressure

PASMC:

Pulmonary artery smooth muscle cell

PDE5:

Phosphodiesterase 5

PDGF:

Platelet-derived growth factor

PECAM:

Platelet endithelial cell adhesion molecule

PET:

Position emission tomography

PH:

Pulmonary hypertension

Pim1:

Proviral integration site for Moloney murine leukemia 1

PPAR:

Peroxisome proliferator activated receptor (gamma γ or alpha α)

Q:

Pefusion

RDW:

Red blood cell distribution width

RHC:

Right heart catheterization

ROS:

Reactive oxygen species

RV:

Right ventricle

RVH:

Right ventricle hypertrophy

SPECT:

Single photon emission computed tomography

SOD:

Superoxyde dismutase

STAT3:

Signal transducer and activator of transcription 3

TAPSE:

Tricuspid annular plane systolic excursion

TGFβ:

Tranforming growth factor beta

TXA2 :

Thromboxane A2

V:

Ventilation

vWF:

Plasma von Willebrand factor

WHO:

World Health Organization

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Acknowledgments

M.H.J. is supported by CAPES (Brazilian Research Agency) and by Laval University. J.M. is a recipient of a Graduate Scholarship from the Canadian Institutes of Health Research CIHR) and A.C. received a graduate scholarship from La Société Québécoise d’Hypertension Artérielle (SQHA). This work was support by Canada Research Chairs (CRC) and by Canadian Institutes of Health Research (CIHR) to S.B. We would like to thank Dr. Richard Poulin for editorial help in processing this manuscript.

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  1. Pulmonary Hypertension Research Group, Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Ste-Foy, Québec, QC, G1V 4G5, Canada

    Marjorie Barrier, Jolyane Meloche, Maria Helena Jacob, Audrey Courboulin, Steeve Provencher & Sébastien Bonnet

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  1. Marjorie Barrier
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  2. Jolyane Meloche
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  3. Maria Helena Jacob
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  4. Audrey Courboulin
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  6. Sébastien Bonnet
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Correspondence to Sébastien Bonnet.

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Barrier, M., Meloche, J., Jacob, M.H. et al. Today’s and tomorrow’s imaging and circulating biomarkers for pulmonary arterial hypertension. Cell. Mol. Life Sci. 69, 2805–2831 (2012). https://doi.org/10.1007/s00018-012-0950-4

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  • DOI: https://doi.org/10.1007/s00018-012-0950-4

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