Targeting Endothelial PDK4-EndoMT Feedback Loop Mitigates the Development of Thoracic Aortic Dissection in Mice - PubMed
3 hours ago
- #PDK4
- #Endothelial-to-Mesenchymal Transition
- #Thoracic Aortic Dissection
- Thoracic aortic dissection (TAD) is a life-threatening condition with high morbidity and mortality.
- Endothelial-to-mesenchymal transition (EndoMT) plays a critical role in TAD development.
- PDK4 (pyruvate dehydrogenase kinase 4) was identified as a key driver of EndoMT in TAD.
- Transcriptomic profiling and immunofluorescence analysis were used in human and murine models to study EndoMT.
- The transcription factor SNAI1 directly activates PDK4 expression, creating a PDK4-EndoMT feedback loop.
- EC-specific Pdk4 overexpression induced aortic dissection, while knockdown or inhibition with dichloroacetate mitigated TAD progression.
- PDK4 is highlighted as a promising therapeutic target for TAD.