Abstract 15544: Implication of the Histone Methyltransferase “G9a” in Pulmonary Arterial Hypertension

• Published in: Circulation (New York, N.Y.) N.Y.), 2020-11, Vol.142 (Suppl_3 Suppl 3), p.A15544-A15544
• Main Authors: awada, Charifa, Habbout, Karima, Nadeau, Valerie, Breuils-Bonnet, Sandra, Paulin, Roxane, Provencher, Steeve, Bonnet, Sebastien, BOUCHERAT, Olivier
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.15544

RationalePulmonary arterial hypertension (PAH) is a cardiopulmonary disorder characterized by elevation of pulmonary arterial (PA) pressure and premature death. PA smooth muscle cells (PASMCs) from PAH patients present a cancer-like hyperproliferative and apoptosis-resistant phenotype contributing to remodeling of distal PAs. Although epigenetic alterations contribute to PAH development, one important challenge is defining which genes are the drivers. A growing body of literature points to the role of an epigenetic factor called G9a in cancer pathogenesis. Indeed, G9a is a histone methyltransferase overexpressed in many cancers promoting cell proliferation and survival. Given the similarities between PAH and cancer, it is of interest to determine whether G9a is implicated in PAH. We thus hypothesized that G9a inhibition reduces the pro-proliferative and apoptosis resistance phenotype of PAH-PASMCs. Methods and ResultsUsing Western blot (WB) and immunofluorescence (IF), we showed that G9a is overexpressed in distal PAs and isolated PASMCs from PAH patients (n= 6-14, p