Integrative multi-omics and machine learning reveal glycolysis-related biomarkers driving vascular remodeling in pulmonary arterial hypertension - PubMed
3 hours ago
- #pulmonary arterial hypertension
- #vascular remodeling
- #glycolysis
- Study investigates aerobic glycolysis in pulmonary arterial hypertension (PAH) and its role in vascular remodeling and endothelial-mesenchymal transition (EndMT).
- Integration of bulk and single-cell transcriptomic data from hypoxia-induced PAH rat models via a multi-algorithm machine-learning pipeline (LASSO, BORUTA, SVM-RFE).
- Identified five glycolysis-related biomarkers: Cxcr4, Pfkfb3, Rgcc, MGC105649, and Mt2A, with PFKFB3 and MT2A as core regulators linking glycolysis to EndMT.
- Single-cell and pseudotime analyses showed endothelial cells transition to mesenchymal-like phenotypes under hypoxia, with increased glycolytic signaling.
- Validation in vivo and in vitro confirmed elevated PFKFB3 and MT2A expression, with hypoxia and lactate promoting endothelial proliferation.
- Findings provide a glycolysis-driven EndMT axis as a mechanism for pulmonary vascular remodeling, highlighting PFKFB3 and MT2A as potential therapeutic targets.