Voloshyna I, Hussaini SM, Reiss AB. Resveratrol in cholesterol metabolism and atherosclerosis. J Med Food. September 2012;15(9):763-773.
Cardiovascular disease is a serious condition affecting global health. The "French Paradox" refers to an unexpectedly low occurrence of cardiovascular disease in France as compared to the United States. It is theorized that this may be due to differences in red wine (from grapes [Vitis vinifera]) consumption; a bioactive compound in wine, resveratrol, has been a focus of research in cardiovascular disease prevention, among other bioactivities. This review addresses the potential cardioprotective activity of resveratrol and focuses on impacts of cholesterol metabolism.
Resveratrol is a polyphenol stilbene and aids in warding off infection in plants. The trans form of the compound is considered to be more bioactive. This compound has good absorption but low bioavailability, with a plasma "peak concentration" at 30 minutes after ingestion. The metabolites of resveratrol are glucuronide and sulfate conjugates that may also be bioactive. In addition, resveratrol is also lipophilic; this could result in the compound being present in larger concentrations biologically than those detected in blood samples.
The metabolism of lipids in macrophages plays a large role in the condition of high cholesterol. Resveratrol is reported to modulate protein networks involved in this process. It is thought that the decrease of macrophage lipid metabolism may be a pharmaceutical target for alleviating atherosclerosis. The authors' previous work and other studies show that resveratrol may assuage atherosclerosis by activating reverse cholesterol transporters like peroxisome proliferator-activated receptor gamma (PPARγ), liver X receptor alpha (LXRα), 27-hydroxylase, and the adenosine triphosphate (ATP) binding cassette (ABC) A1 transporter; this is thought to inhibit the buildup of cholesterol. Many cellular processes, including the metabolism of adipose tissue, are regulated by the PPAR family of transcription factors, and a study showed that resveratrol prevented strokes in mice via modulating PPAR activation.
The ABC transporters aid in controlling cholesterol concentrations by transporting lipids. Resveratrol has been shown to activate ABCA1 and ABCG1, as well as to induce cholesterol transport in another study. An additional study also points to the inhibition of enzymes responsible for macrophage lipid ingestion. In vitro, resveratrol decreased the activity of a cytokine known as interferon-gamma (IFN-γ), an inhibitor of ABCA1 and ABCG1 transporter activity. Another study showed that resveratrol alleviates the effects of IFN-γ, suggesting a potential mechanism for atherosclerosis prevention.
Resveratrol has recently been shown to indirectly modulate activity of sirtuin 1 (SIRT1),1 an enzyme that controls the activity of many signaling agents, including PPARs. Resveratrol has also been found to alleviate the dysfunction of endothelial cells but has also been thought to inhibit vessel development; this may render resveratrol inappropriate for use with those suffering from certain health conditions. Adenosine monophosphate-activated protein kinase (AMPK) regulates a large amount of cell signaling and has been found to be activated by resveratrol. Resveratrol has also been shown to limit the accumulation of lipids by stimulating SIRT1 and AMPK activity, both in vitro and in vivo.
In vitro, resveratrol was found to both modulate cholesterol flow and reduce lipid peroxide concentrations. It has also been shown to have in vitro antioxidant activity and to activate endogenous antioxidant defense enzymes. Additional studies have reported resveratrol limits platelet aggregation and increases apoptosis and that this bioactivity is retained in patients resistant to aspirin. In a clinical study, this compound increased vasodilation in the context of heart disease and, in another clinical trial, showed a significant beneficial effect on endothelial function.
In conclusion, resveratrol has been shown to be an antioxidant and to affect both vasodilation and platelet aggregation, making it a robust candidate for further clinical research into cardiovascular disease treatment or prevention. It is mentioned that this compound is safe; no adverse side effects are specifically discussed. More clinical studies are needed to determine the specifics of potential resveratrol efficacy in cardiovascular disease therapy.
—Amy C. Keller, PhD
- Park S-J, Ahmad F, Philp A, et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. February 3, 2012;148(3):421-433.