Cyclic guanosine monophosphate-protein kinase G signaling attenuates aortic valve calcification through ULK1-mediated autophagy - PubMed
7 hours ago
- #cGMP-PKG signaling
- #aortic valve calcification
- #autophagy
- Cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling is suppressed in calcified aortic valves.
- Serum cGMP levels inversely correlate with calcification severity in patients with calcific aortic valve disease (CAVD).
- PKGI haploinsufficiency worsens aortic valve calcification in a CAVD mouse model.
- Pharmacological activation of cGMP-PKG signaling (e.g., by vericiguat, BNP, or sildenafil) reduces calcium deposition in human valvular interstitial cells (VICs).
- Vericiguat shows the strongest anti-calcification effect and alleviates disease progression in CAVD models.
- PKGI enhances autophagy by phosphorylating ULK1 at Ser556, preserving mitochondrial function and reducing oxidative stress.
- The study highlights vericiguat as a potential therapy for CAVD.