Schisandrol B inhibits calcification of aortic valve by targeting p53 related inflammatory and senescence - 21/08/24
Abstract |
Calcific aortic valve disease (CAVD) primarily involves osteogenic differentiation in human aortic valve interstitial cells (hVICs). Schisandrol B (SolB), a natural bioactive constituent, has known therapeutic effects on inflammatory and fibrotic disorders. However, its impact on valve calcification has not been reported. We investigated the effect of SolB on osteogenic differentiation of hVICs. Transcriptome sequencing was used to analyze potential molecular pathways affected by SolB treatment. The study also included an in vivo murine model using aortic valve wire injury surgery to observe SolB's effect on valve calcification. SolB inhibited the osteogenic differentiation of hVICs, reversing the increase in calcified nodule formation and osteogenic proteins. In the murine model, SolB significantly decreased the peak velocity of the aortic valve post-injury and reduced valve fibrosis and calcification. Transcriptome sequencing identified the p53 signaling pathway as a key molecular target of SolB, demonstrating its role as a molecular glue in the mouse double minute 2 (MDM2)-p53 interaction, thereby promoting p53 ubiquitination and degradation, which further inhibited p53-related inflammatory and senescence response. These results highlighted therapeutic potential of SolB for CAVD via inhibiting p53 signaling pathway and revealed a new molecular mechanism of SolB which provided a new insight of theraputic mechanism for CAVD.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | SolB reversed osteogenic differentiation in hVICs. |
• | SolB reduces valvular calcification in aortic valve injury murine model. |
• | SolB enhanced MDM2-p53 interaction and reduced p53 related inflammation and senescence. |
• | SolB is a potential pharmacotherapy for CAVD. |
Abbreviations : CAVD, HVICs, SolB, SAVR, TAVR, TGFβ1, NF-κB, MDM2, WI, ALP, Runx2, TNF-α, IL-, MCP-1, KEGG, DEGs, GO, DMEM, GAPDH, FBS, OPN, HE, PBS, DPP4, DAPI, SEM, OM
Keywords : CAVD, Schisandrol B, Osteogenic differentiation, p53 signaling pathway, MDM2-p53 interaction
Plan
Vol 178
Article 117241- septembre 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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