Disruption of sphingolipid metabolism triggers lung vascular inflammation and aging-like changes under hypoxia through VDAC1-mediated mitochondrial DNA release - PubMed
4 hours ago
- #mitochondrial dysfunction
- #sphingolipids
- #hypoxia
- Disruption of sphingolipid metabolism in the lung under hypoxia leads to vascular inflammation and aging-like changes.
- Hypoxia increases C24-Ceramide (Cer) and its synthase (CERS2) in pulmonary microvascular endothelial cells (PMVECs).
- C24-Cer binds to VDAC1, promoting mitochondrial DNA (mtDNA) release and activating the cGAS-STING pathway.
- Inhibition of C24-Cer or VDAC1 oligomerization reduces mtDNA release and alleviates inflammation and aging-like changes.
- The study suggests a potential therapeutic target for high-altitude hypoxia-related vascular diseases.