High-Salt Diet-Induced Endothelial Dysfunction Is Mediated by Cellular Senescence

Area of Science:

• Cardiovascular Research
• Vascular Biology
• Aging Research

Background:

• High salt (HS) intake is a cardiovascular risk factor.
• Mechanisms linking HS to endothelial dysfunction are unclear.
• This study investigates HS-induced vascular senescence and dysfunction.

Purpose of the Study:

• To determine if HS induces vascular senescence and dysfunction.
• To assess if targeting senescent cells can prevent these effects.
• To explore the role of immune activation and IL16 signaling.

Main Methods:

• Mice were fed a high-salt diet (HSD) for 14 or 28 days.
• Vascular function was assessed using wire myography.
• Senescence markers (p21, p16) and inflammatory cytokines (IL-6, IL-1β, IL16) were measured.
• Senolytic drug navitoclax was administered to test reversibility.

Main Results:

• A 28-day HSD induced endothelial dysfunction and vascular senescence.
• Navitoclax treatment reduced senescence markers and improved vascular function.
• HSD increased inflammatory gene expression and circulating IL16 levels.
• Recombinant IL16 induced endothelial dysfunction and senescence markers in vitro.

Conclusions:

• Prolonged HSD intake causes vascular senescence and dysfunction, driven by immune activation.
• Senolytic therapy effectively prevents HSD-induced vascular dysfunction.
• Targeting senescence or IL16 signaling offers potential therapeutic strategies for salt-sensitive vascular diseases.