PT  - JOURNAL ARTICLE
AU  - Natalia Gambaryan
AU  - Christophe Guignabert
AU  - Ly Tu
AU  - Frederic Perros
AU  - Ian Adcock
AU  - Marc Humbert
AU  - Stephen Wort
TI  - The role of bromodomain-containing protein 4 in the constitutive activation of nuclear factor-kappa B in endothelial cells from patients with pulmonary arterial hypertension
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3177
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3177.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3177.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - BACKGROUNDPulmonary arterial hypertension (PAH) is characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and death. Pulmonary endothelial cells (P-ECs) are well known as producers of cytokines and chemokines essential in the recruitment of inflammatory cells to the lungs, and a constitutive activation of the nuclear factor-kappa B (NF-κB) signaling pathway in P-ECs has been recently described in PAH. RelA lysine-310 acetylation of NF-κB generates a specific docking sites for bromodomain-containing protein 4 (Brd4). We hypothesize that Brd4 through an NF-κB-dependent mechanism contributes to the hyperproliferative and proinflammatory phenotype in P-ECs in patients with PAH.AIMThe aim of the study was to evaluate the in vitro effect of Brd4 inhibition using the selective inhibitor JQ1 on proliferation and apoptosis in P-ECs.METHODS AND RESULTSThe effect of JQ1 on P-ECs proliferation was established by assessing the incorporation of BrdU. We found a strong anti-proliferative effect of JQ1 in P-ECs (Fig. 1A). We also demonstrated that JQ1 induces caspase-3 activity in P-ECs resulting in increased apoptosis (Fig. 1B).CONCLUSIONSelective Brd4 inhibitors, such as JQ1, may represent novel therapeutic agents for the treatment of PAH. Further work is necessary to explore this hypothesis.