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Olfactory receptors in pulmonary arterial hypertension: A novel pathway of vascular remodeling?

Audrey Courboulin, Guenhaël Sanz, Sandra Breuils-Bonnet, Marceau Quatredeniers, Matthieu Vocelle, Mathilde Lafond, Frédéric Perros, Sébastien Bonnet, Edith Pajot-Augy, Marc Humbert, Sylvia Cohen-Kaminsky
European Respiratory Journal 2015 46: PA2431; DOI: 10.1183/13993003.congress-2015.PA2431
Audrey Courboulin
1Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Guenhaël Sanz
2UR1197, INRA, Jouy-en-Josas, France
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Sandra Breuils-Bonnet
3Groupe de Recherche en Hypertension Artérielle Pulmonaire, CRIUCPQ, Québec, Canada
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Marceau Quatredeniers
4Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Matthieu Vocelle
5Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Mathilde Lafond
6Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Frédéric Perros
7Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Sébastien Bonnet
8Groupe de Recherche en Hypertension Artérielle Pulmonaire, CRIUCPQ, Québec, Canada
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Edith Pajot-Augy
9UR1197, INRA, Jouy-en-Josas, France
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Marc Humbert
10Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Sylvia Cohen-Kaminsky
11Inserm U999 - Université Paris-Sud, Centre Chirurgical Marie Lannelongue, Le Plessis Robinson, France
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Abstract

Pulmonary arterial hypertension (PAH) is due to progressive obstruction of pulmonary arteries, thus leading to right heart failure and death. Breath volatile organic compounds (VOCs) can discriminate PAH and controls. Thus, a unique breath-print of PAH is detected using an artificial nose. VOCs target olfactory receptors (ORs) in olfaction. Interestingly, ORs are detected in peripheral tissues not related to olfaction and their deregulation is associated to cancer development. PSGR, encoded by the OR51E2 gene, is one of the ORs. Because vascular cells in PAH exhibit properties of cancer cells, we propose the ground-breaking hypothesis that ORs participate to vascular remodeling leading to PAH.

Thus we aim to determine whether a deregulated expression and function of the pulmonary vascular PSGR could participate to the pathological phenotype of vascular cells, and its potential use as a novel therapeutic target in PAH.

PSGR gene and protein expression were assessed in total lung, distal pulmonary arteries and PASMCs from PAH patients compared to controls using qRT-PCR and western blot. We evaluated proliferation (Ki67) and apoptosis (TMRM) after siRNA-directed silencing of PSGR expression in PASMCs.

We demonstrate that PSGR expression is significantly increased (50%) in PASMC, in total lung and isolated pulmonary arteries from PAH patients compared to controls. PSGR silencing in PAH-PASMCs decreased both cell proliferation (20%) and resistance to apoptosis (25%).

This deregulated OR expression in PAH PASMCs opens a new avenue in PAH pathophysiology. The whole spectrum of ORs is currently investigated using microarrays and deregulated ORs will be evaluated both in vitro and in vivo.

  • Pulmonary hypertension
  • Cell biology
  • Treatments
  • Copyright ©ERS 2015
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Olfactory receptors in pulmonary arterial hypertension: A novel pathway of vascular remodeling?
Audrey Courboulin, Guenhaël Sanz, Sandra Breuils-Bonnet, Marceau Quatredeniers, Matthieu Vocelle, Mathilde Lafond, Frédéric Perros, Sébastien Bonnet, Edith Pajot-Augy, Marc Humbert, Sylvia Cohen-Kaminsky
European Respiratory Journal Sep 2015, 46 (suppl 59) PA2431; DOI: 10.1183/13993003.congress-2015.PA2431

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Olfactory receptors in pulmonary arterial hypertension: A novel pathway of vascular remodeling?
Audrey Courboulin, Guenhaël Sanz, Sandra Breuils-Bonnet, Marceau Quatredeniers, Matthieu Vocelle, Mathilde Lafond, Frédéric Perros, Sébastien Bonnet, Edith Pajot-Augy, Marc Humbert, Sylvia Cohen-Kaminsky
European Respiratory Journal Sep 2015, 46 (suppl 59) PA2431; DOI: 10.1183/13993003.congress-2015.PA2431
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More in this TOC Section

  • Effects of apoptosis signal- regulating kinase 1 (ASK1) inhibition in experimental pressure overload-induced right ventricular dysfunction
  • LSC Abstract – Glutamatergic signaling through pulmonary vascular NMDA receptors in pulmonary hypertension
  • CD163 is expressed and modulated in human pulmonary artery smooth muscle cells: Implications for pulmonary artery hypertension
Show more 4.3 Pulmonary Circulation and Pulmonary Vascular Disease

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