Elevated Fibroblast Growth Factor 23 Impairs Endothelial Function through the NF-κB Signaling Pathway

Area of Science:

• Cardiovascular Biology
• Endothelial Function Research
• Molecular Medicine

Background:

• Fibroblast growth factor 23 (FGF23) roles in endothelial dysfunction are debated.
• Limited population-based data exists on FGF23 and endothelial dysfunction in coronary artery disease (CAD).

Purpose of the Study:

• To investigate the association between FGF23 and endothelial dysfunction in CAD patients.
• To elucidate the in vitro mechanisms by which FGF23 affects endothelial cells.

Main Methods:

• Clinical study of 321 CAD patients assessing flow-mediated dilation (FMD), serum FGF23, nitric oxide (NO), and endothelin-1 (ET-1).
• In vitro experiments using human umbilical vein endothelial cells (HUVECs) to assess apoptosis, migration, reactive oxygen species (ROS), and NF-κB pathway activation.

Main Results:

• CAD patients with severe endothelial dysfunction (FMD <2%) had significantly higher FGF23 levels.
• FGF23 levels negatively correlated with NO and positively with ET-1.
• In vitro, FGF23 increased oxidative stress, impaired NO bioavailability, promoted HUVEC apoptosis, reduced migration, and activated the NF-κB pathway.

Conclusions:

• Elevated FGF23 is clinically associated with endothelial dysfunction in CAD.
• FGF23 impairs endothelial function by activating the NF-κB signaling pathway, leading to oxidative stress and cellular damage.