Unconventional mechanisms of resveratrol in atherosclerosis prevention and management

Atherosclerosis is a progressive inflammatory disease and a major contributor to cardiovascular disease. Resveratrol (RES), a polyphenolic compound found in grapes and red wine, has been widely investigated for its protective effects on cardiovascular health. This review summarizes the mechanisms through which RES attenuates atherosclerosis, including its anti-inflammatory, antioxidant, and lipid-modulating effects. Experimental evidence indicates that RES inhibits nuclear factor kappa-light-chain-enhancer of activated B cells signaling, thereby reducing the expression of adhesion molecules such as vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 and limiting immune cell infiltration into the arterial wall. Additionally, it counteracts oxidative stress by enhancing antioxidant enzyme activity and preventing low-density lipoprotein oxidation, a key event in foam cell formation. RES also promotes cholesterol efflux through adenosine triphosphate-binding cassette transporters, supporting high-density lipoprotein-mediated reverse cholesterol transport. Findings from in vitro, animal, and clinical studies suggest that RES can reduce atherosclerotic plaque development, improve endothelial function, and modulate lipid metabolism.