Abstract 12681: Implication of Aurora Kinase B in Pulmonary Arterial Hypertension

• Published in: Circulation (New York, N.Y.) N.Y.), 2021-11, Vol.144 (Suppl_1), p.A12681-A12681
• Main Authors: Sauvaget, Melanie, Lemay, Sarah-eve, Breuils Bonnet, Sandra, Orcholski, Mark, Mkannez, Ghada, Schimauchi, Kana, Paulin, Roxane, Potus, François, BOUCHERAT, Olivier, Bonnet, Sebastien
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.144.suppl_1.12681

ObjectivePulmonary arterial hypertension (PAH) is a vascular disease characterized by a progressive remodelling of pulmonary arteries (PAs). This leads to an elevation in PA pressure and resistance, leading to right heart failure and death. Nowadays, it is recognized that PA smooth muscle cells (PASMCs) are key actors in the histopathological changes in PAH. As seen in cancer cells, PASMCs exhibit a pro-proliferative and anti-apoptotic cancer-like phenotype, sustained by an important metabolic switch known as Warburg effect. Aurora kinase B (AURKB) is strongly involved in cell proliferation, apoptosis and metabolism by controlling cell cycle activation and mitochondrial functions. Previous research has shown that AURKB is overexpressed in various human cancers and its inhibition repressed tumor progression both in vivo and in vitro, suggesting that it could be a novel therapeutic target in PAH. We thus hypothesized that AURKB is upregulated in PAH and contributes to PAH-PASMCs proliferation and resistance to apoptosis, inhibition of which may reverse PA remodeling. Methods/ResultsUsing Western blot (WB), we demonstrated a FOXM1-dependent upregulation of AURKB in PASMCs isolated from PAH patients compared to controls (p