Basic fibroblast growth factor inhibits aortic valvular interstitial cells calcification via Notch1 pathway

Area of Science:

• Cardiovascular Biology
• Cellular Biology
• Biochemistry

Background:

• Calcific aortic valve disease (CAVD) involves abnormal valvular interstitial cell (VIC) activation and transdifferentiation.
• Understanding the molecular mechanisms regulating VIC osteogenic differentiation is crucial for CAVD therapeutics.

Purpose of the Study:

• To investigate the role and mechanism of basic fibroblast growth factor (BFGF) in regulating VIC osteogenic differentiation.
• To explore BFGF's potential as a therapeutic agent for CAVD.

Main Methods:

• Porcine VICs were cultured with or without BFGF under osteogenic induction.
• Assessed VIC morphology, viability, calcium deposition (Alizarin Red S), and osteogenic marker expression (Runx2, osteopontin, Sp7) via Western blot and qPCR.
• RNA sequencing identified gene expression changes and the Notch1 signaling pathway.

Main Results:

• BFGF supplementation significantly downregulated calcium deposition and osteogenic marker expression in VICs.
• RNA sequencing identified the Notch1 signaling pathway as a key mediator.
• Inhibition of Notch1 signaling abolished BFGF's calcification-inhibitory effects.

Conclusions:

• BFGF exerts an inhibitory effect on VIC osteogenic differentiation and calcification.
• The Notch1 signaling pathway is a critical mechanism through which BFGF regulates CAVD progression.
• BFGF represents a potential therapeutic target for managing CAVD.