Resveratrol Mediates Anti-Atherogenic Actions In Vitro and in LDL Receptor-Deficient Mice Fed a High-Fat Diet via...

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Pharmacology

Background:

• Current pharmacotherapies for atherosclerotic cardiovascular disease (ASCVD) have limitations, including residual risk and adverse effects.
• Nutraceuticals like resveratrol (RSV) offer a potentially safer alternative, but their anti-atherogenic mechanisms require further elucidation.

Purpose of the Study:

• To investigate the impact of resveratrol (RSV) on key atherosclerosis-associated processes in various cell types in vitro and in LDL receptor-deficient mice in vivo.
• To uncover the molecular mechanisms underlying RSV's anti-atherogenic effects.

Main Methods:

• In vitro studies using monocytes, macrophages, endothelial cells, and smooth muscle cells.
• In vivo studies utilizing LDL receptor-deficient mice on a high-fat diet.
• RNA-sequencing of thoracic aorta to identify mediating genes and pathways.

Main Results:

• RSV improved plasma lipid profiles and peripheral blood lymphoid cells in vivo.
• RSV reduced plaque inflammation (decreased macrophage and T cell content) and enhanced plaque stability (increased smooth muscle cells and collagen).
• In vitro, RSV inhibited monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion.

Conclusions:

• RSV exhibits significant anti-atherogenic properties, including antioxidant, anti-inflammatory, and plaque-stabilizing effects.
• The study provides novel mechanistic insights into RSV's actions against atherosclerosis.
• RSV warrants further investigation in human clinical trials for ASCVD treatment.