# Resveratrol Mediates Anti-Atherogenic Actions In Vitro and in LDL Receptor-Deficient Mice Fed a High-Fat Diet via Antioxidant, Anti-Inflammatory and Plaque-Stabilising Activities

## TL;DR

Resveratrol shows anti-atherogenic effects in cells and mice by reducing inflammation, stabilizing plaques, and improving lipid profiles.

## Contribution

This study reveals novel molecular mechanisms of resveratrol's anti-atherogenic actions in multiple cell types and in vivo models.

## Key findings

- RSV reduced plaque inflammation and increased plaque stability in LDL receptor-deficient mice.
- RSV inhibited monocyte migration, inflammasome activation, and reactive oxygen species production in vitro.
- RNA-sequencing identified key genes and pathways involved in RSV's anti-atherogenic effects.

## Abstract

Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials.