Pro-proliferative and inflammatory signaling converge on the FoxO1 transcription factor in pulmonary hypertension – a new therapeutic approach
R Savai, HM Al-Tamari, D Sedding, B Kojonazarov, C Muecke, R Teske, MR Capecchi, N Weissmann, F Grimminger, W Seeger, RT Schermuly, S Savai Pullamsetti · Pneumologie · 2015 · Heft 02
Bibliografische Angaben
Zusammenfassung
Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that FoxO1 was downregulated (expression) and inactivated (phosphorylation, nuclear exclusion) in vessels/PASMCs of human and experimental PH lungs. This was reproduced by ex vivo exposure of PASMCs to growth factors and inflammatory cytokines. Pharmacological inhibition and genetic ablation of FoxO1 in PASMCs reproduced PH features in vitro and in vivo. Pharmacologi…
