Pulmonary vascular disease & thromboembolism
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1
An erratum to this article was published (Circulation, 8 Jan 2019 ↗)
Authors' conclusion
CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.
Study context
- Population
- Bovine and human adventitial fibroblasts and hypoxic mouse lung tissues (pulmonary hypertension)
- Comparison
- CtBP1 inhibition vs no inhibition
Main finding
As reported in the abstract
- PH-Fibs displayed aerobic glycolysis under normoxia, with increased free NADH and NADH/NAD+ ratios
- CtBP1 expression increased in vivo and in vitro in adventitial fibroblasts of idiopathic PAH humans, pulmonary hypertension (PH) animals and cultured PH-Fibs
- MTOB or CtBP1 siRNA upregulated p15, p21, NOXA and PERP, attenuated proliferation, corrected glycolytic reprogramming and augmented HMOX1 transcription
- CtBP1 directly binds the HMOX1 promoter (ChIP)
- MTOB in hypoxic mice decreased glycolysis and inflammatory gene expression, attenuated proliferation, and suppressed macrophage numbers and distal pulmonary vascular remodeling
Original publication
Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1. Circulation. Published 25 August 2016. doi:10.
Summarised from the published abstract; every number is checked against it