Valvular & structural heart disease
Targeting Sphingosine-1-Phosphate Signaling to Prevent the Progression of Aortic Valve Disease
Authors' conclusion
Increased systemic or local S1P levels lead to increased valvular calcification.
Study context
- Population
- Mice with wire injury-induced aortic valve disease (AVD); human valvular interstitial cells; human explanted aortic valves from patients undergoing aortic valve replacement
- Comparison
- Pharmacological and genetic modulation of S1P production, degradation and receptor signaling in a murine AVD model
- Outcome
- AVD progression and cardiac function
Main finding
As reported in the abstract
- Raising S1P by S1P lyase inhibition vastly enhanced AVD progression and impaired cardiac function
- Low S1P from SphK1 deficiency potently attenuated AVD progression
- S1PR2-deficient mice protected against AVD progression and its deterioration by high S1P
- Pharmacological S1PR2 inhibition after wire injury prevented AVD development
- Biomechanical stretch stimulated S1P production by SphK1 in human valvular interstitial cells; S1P/S1PR2 signaling induced osteoblastic differentiation and calcification via RUNX2/OPG and GSK3β-Wnt-β-catenin
- In patients with AVD, stenotic valves exposed to high wall shear stress had higher S1P content and increased SphK1 expression
Original publication
Targeting Sphingosine-1-Phosphate Signaling to Prevent the Progression of Aortic Valve Disease. Circulation. Published 21 October 2024. doi:10.
Summarised from the published abstract; every number is checked against it