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Haploid genetic screening identifies a novel regulator of BMPR2
Pulmonary arterial hypertension (PAH), is characterised by profound remodelling of small pulmonary arteries, leading to increased pulmonary arterial pressures and premature death by right heart failure. Heterozygous germ-line mutations in the bone morphogenetic protein type II receptor (BMPR2) cause ~70% of familial PAH and ~20% of idiopathic PAH cases. The majority of mutations lead to haploinsufficiency but crucially, regardless of the presence of mutation, lung BMPR2 expression is reduced in all forms of PAH. Therefore, restoration of BMPR2 levels is an important therapeutic target. We previously showed that BMPR2 ubiqu...
Source: European Respiratory Journal - October 28, 2020 Category: Respiratory Medicine Authors: Dunmore, B., Burr, S., Upton, P., Nathan, J., Morrell, N. Tags: Pulmonary hypertension Source Type: research

The BRD4-PLK1 Axis Drives Vascular Remodeling in PAH
Conclusion: We demonstrate that the BRD4/PLK1 axis is increased in human PAH and represents a promising therapeutic target.
Source: European Respiratory Journal - November 19, 2018 Category: Respiratory Medicine Authors: Boucherat, O., Tremblay, E., Martineau, S., Jahagirdar, R., Kulikowski, E., Provencher, S., Bonnet, S. Tags: Pulmonary hypertension Source Type: research

PSGR olfactory receptor: A new potential target in pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is a rare progressive disease due to distal vascular remodeling, leading to right heart failure and death. PSGR is an olfactory receptor (OR) that has been recently detected in peripheral tissues. Moreover, PSGR overexpression is associated with pro-proliferative phenotype in prostate cancer. Since PAH vascular cells are characterized by cancer-like over-proliferation, we hypothesized that PSGR might participate in the vascular remodeling leading to PAH.Here we aimed to determine whether upregulation of PSGR is implicated in PAH pathological phenotype, and to explore PSGR as a novel th...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Courboulin, A., Quatredeniers, M., Sanz, G., Breuils-Bonnet, S., Vocelle, M., Lafond, M., Perros, F., Bonnet, S., Pajot-Augy, E., Humbert, M., Cohen-Kaminsky, S. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Diseases Source Type: research

Olfactory receptors in pulmonary arterial hypertension: A novel pathway of vascular remodeling?
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-breakin...
Source: European Respiratory Journal - October 30, 2015 Category: Respiratory Medicine Authors: Courboulin, A., Sanz, G., Breuils-Bonnet, S., Quatredeniers, M., Vocelle, M., Lafond, M., Perros, F., Bonnet, S., Pajot-Augy, E., Humbert, M., Cohen-Kaminsky, S. Tags: 4.3 Pulmonary Circulation and Pulmonary Vascular Disease Source Type: research