Butyrate protects endothelial function through PPARδ/miR-181b signaling

Area of Science:

• Cardiovascular Biology
• Molecular Medicine
• Nutritional Science

Background:

• Cardiovascular diseases like atherosclerosis are a major health concern.
• Butyrate, a short-chain fatty acid, shows promise in treating cardiovascular conditions.
• The precise mechanisms behind butyrate's beneficial effects, particularly on endothelial dysfunction, are not fully understood.

Purpose of the Study:

• To investigate the protective effects of butyrate on endothelial dysfunction in atherosclerosis.
• To elucidate the underlying molecular mechanisms, focusing on the role of PPARδ and miR-181b.

Main Methods:

• Atherosclerosis models were created in ApoE knockout mice fed a high-fat diet and treated with sodium butyrate.
• Ex vivo experiments utilized isolated thoracic aorta rings from wild-type and PPARδ knockout mice stimulated with IL-1β.
• Endothelial cells were used to assess reactive oxygen species (ROS) production, NADPH oxidase 2 (NOX2) expression, and miR-181b regulation.

Main Results:

• Butyrate treatment improved endothelium-dependent relaxations in atherosclerotic aortas and protected against IL-1β-induced dysfunction.
• The protective effects of butyrate were dependent on Peroxisome proliferator-activated receptor delta (PPARδ).
• Butyrate reduced IL-1β-induced ROS production and NOX2 expression in endothelial cells, mediated by the PPARδ/miR-181b pathway.

Conclusions:

• Butyrate ameliorates endothelial dysfunction in atherosclerosis by suppressing NOX2 expression and ROS production.
• The mechanism involves the activation of the PPARδ/miR-181b signaling pathway.
• Butyrate represents a potential therapeutic agent for preventing and treating atherosclerosis and related cardiovascular diseases.