Transforming growth factor-β regulates endothelial function during high salt intake in rats

Area of Science:

• Cardiovascular Biology
• Molecular Signaling
• Endothelial Function

Background:

• Dietary salt intake stimulates endothelial transforming growth factor-β (TGF-β) production.
• The functional impact of TGF-β on endothelial cells requires further elucidation.

Purpose of the Study:

• To investigate the functional significance of increased TGF-β on endothelial cell function under high salt conditions.
• To identify downstream signaling pathways regulated by TGF-β in endothelial cells.

Main Methods:

• Rats were fed high (8.0%) or low (0.3%) salt diets, followed by treatment with a TGF-β receptor I inhibitor.
• Endothelial cell signaling pathways, including Smad2, PTEN, Akt, and NOS3 phosphorylation, were analyzed.
• Experiments in human umbilical vein endothelial cells and macrovascular endothelial cells explored PTEN and TGF-β1 interactions.

Main Results:

• High salt intake increased endothelial phosphorylated Smad2 and decreased PTEN levels.
• Downstream signaling, including phosphorylated Akt and NOS3, was elevated in high-salt-fed rats.
• Inhibition of TGF-β receptor I reversed high-salt-induced signaling changes.
• Reduced PTEN levels in human cells increased phosphorylated Akt and NOS3.
• TGF-β1 treatment increased phosphorylated NOS3 and NO metabolites, an effect abolished by PTEN knockdown.

Conclusions:

• Increased TGF-β during high salt intake directly reduces endothelial PTEN levels.
• This reduction in PTEN regulates Akt activation and NOS3 phosphorylation.
• A feedback loop involving TGF-β, PTEN, Akt, and NOS3 may mitigate TGF-β's vascular effects.