RUNX2 is stabilised by TAZ and drives pulmonary artery calcification and lung vascular remodelling in pulmonary hypertension due to left heart disease
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View abstract on PubMed
Summary
This summary is machine-generated.Pulmonary hypertension due to left heart disease involves vascular calcification driven by TAZ-dependent stabilization of RUNX2. Inhibiting this TAZ-RUNX2 pathway may offer a new therapeutic strategy for this condition.
Area Of Science
- Cardiovascular Biology
- Molecular Biology
- Pulmonary Hypertension Research
Background
- Vascular calcification is common in chronic disease but its role in pulmonary hypertension due to left heart disease (PH-LHD) is unclear.
- Investigated the role of runt-related transcription factor-2 (RUNX2) and the HIPPO pathway coactivator TAZ in PH-LHD.
- Utilized a rat model of PH-LHD induced by supracoronary aortic banding.
Purpose Of The Study
- To elucidate the role of RUNX2 and TAZ in the osteogenic reprogramming of pulmonary artery smooth muscle cells.
- To determine the mechanisms underlying vascular calcification in PH-LHD.
- To evaluate the therapeutic potential of targeting the TAZ-RUNX2 axis in PH-LHD.
Main Methods
- Collected pulmonary artery samples from patients and rats with PH-LHD.
- Performed genome-wide RNA sequencing and assessed pulmonary artery calcification.
- Utilized protein biochemistry to delineate TAZ and RUNX2 signaling, and tested TAZ/RUNX2 inhibitors in a rat model.
Main Results
- Significant enrichment of ossification and osteoblast differentiation genes, including RUNX2, in PH-LHD pulmonary arteries.
- Pulmonary artery calcification was observed in both patients and rats.
- TAZ and RUNX2 were upregulated and activated, interacting directly in pulmonary artery smooth muscle cells; TAZ inhibition reduced RUNX2 levels via degradation. Inhibition of TAZ or RUNX2 attenuated calcification, vascular remodeling, and PH development in rats.
Conclusions
- PH-LHD is linked to pulmonary artery calcification driven by TAZ-mediated RUNX2 stabilization, promoting osteogenic reprogramming.
- The TAZ-RUNX2 pathway represents a potential therapeutic target for PH-LHD.
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