Restoration of vascular dysfunction resulting from maternal high-fat diet via modulation of the NLRP3/IL-1β axis

Area of Science:

• Cardiovascular Science
• Developmental Biology
• Nutritional Science

Background:

• Maternal diet significantly influences offspring health.
• High-fat diets during pregnancy are linked to adverse cardiovascular outcomes in offspring.
• Endothelial dysfunction and inflammation are key contributors to cardiovascular disease.

Purpose of the Study:

• To investigate the effects of maternal high-fat diet on offspring vascular function and endothelial homeostasis.
• To explore the role of the NLRP3/IL-1β pathway in mediating these effects.
• To assess the therapeutic potential of NLRP3/IL-1β inhibition.

Main Methods:

• Offspring from dams fed a high-fat diet were compared to controls.
• Vascular function, blood pressure, and endothelial homeostasis markers were assessed.
• Levels of reactive oxygen species (ROS) and pro-inflammatory cytokines were measured.
• Intervention with NLRP3 or IL-1β inhibitors was performed.

Main Results:

• Maternal high-fat diet led to elevated offspring blood pressure and impaired aortic vascular function.
• Endothelial homeostasis was disrupted, with increased ROS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10).
• NLRP3 or IL-1β inhibition ameliorated vascular dysfunction, reduced NO production, and decreased inflammation.

Conclusions:

• Maternal high-fat diet induces significant vascular impairments and inflammation in offspring.
• The NLRP3/IL-1β pathway is critically involved in mediating these adverse effects.
• Inhibiting the NLRP3/IL-1β pathway during pregnancy offers a potential strategy to mitigate offspring cardiovascular risks.