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Biol Aujourdhui. 2016;210(2):65-78. doi: 10.1051/jbio/2016010. Epub 2016 Sep 30.

[Towards new targets for the treatment of pulmonary arterial hypertension : Importance of cell-cell communications].

[Article in French]

Author information

1
INSERM UMRS 999, LabEx LERMIT, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis-Robinson, France - Université Paris-Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France.
2
INSERM UMRS 999, LabEx LERMIT, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis-Robinson, France - Université Paris-Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France - Service de Pathologie, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
3
INSERM UMRS 999, LabEx LERMIT, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis-Robinson, France - Université Paris-Sud, Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France - AP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, France.

Abstract

Pulmonary arterial hypertension (PAH) is a disorder in which mechanical obstruction of the pulmonary vascular bed is largely responsible for the rise in mean pulmonary arterial pressure (mPAP), resulting in a progressive functional decline despite current available therapeutic options. There are multiple mechanisms predisposing to and/or promoting the aberrant pulmonary vascular remodeling in PAH, and these involve not only altered crosstalk between cells within the vascular wall but also sustained inflammation and dysimmunity, cell accumulation in the vascular wall and excessive activation of some growth factor-stimulated signaling pathways, in addition to the interaction of systemic hormones, local growth factors, cytokines, and transcription factors. Heterozygous germline mutations in the bone morphogenetic protein receptor, type-2 (BMPR2) gene, a gene encoding a receptor for the transforming growth factor (TGF)-β superfamily, can predispose to the disease. Although the spectrum of therapeutic options for PAH has expanded in the last 20 years, available therapies remain essentially palliative. Over the past decade, however, a better understanding of key regulators of this irreversible remodeling of the pulmonary vasculature has been obtained. New and more effective approaches are likely to emerge. The present article profiles the innovative research into novel pathways and therapeutic targets that may lead to the development of targeted agents in PAH.

PMID:
27687598
DOI:
10.1051/jbio/2016010
[Indexed for MEDLINE]

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