A01
FoxO transcription factors in PH: critical integrators of multiple signaling pathways driving pulmonary vascular and right ventricular remodeling.
Our current findings provide evidence that Forkhead box O (FoxO)-1 nuclear exclusion and transcriptional inactivation trigger the pathologic signaling leading to pulmonary hypertension (PH). To decipher the underlying mechanisms, we now aim to identify the role of FoxO isoforms in different forms of PH, focusing on their regulation at different levels (mRNA, protein and/or post-translational modifications) and their function in chromatin organization. Moreover, we will determine their role in pulmonary arterial/myocardial stiffness and their regulation in compensated and decompensated RV hypertrophy and failure. Overall, we expect that in-depth understanding of FoxO biology will provide novel treatment strategies for the lung vascular and RV abnormalities in PH.
