Abstract
Resveratrol, a natural compound in grapes and red wine, has drawn attention due to potential cardiovascular-related health benefits. However, its effect on vascular inflammation at physiologically achievable concentrations is largely unknown. In this study, resveratrol in concentrations as low as 1 μm suppressed TNF-α-induced monocyte adhesion to human EA.hy926 endothelial cells (ECs), a key event in the initiation and development of atherosclerosis. Low concentrations of resveratrol (0.25–2 μm) also significantly attenuated TNF-α-stimulated mRNA expressions of MCP-1/CCL2 and ICAM-1, which are vital mediators of EC-monocyte adhesion molecules and cytokines for cardiovascular plaque formation. Additionally, resveratrol diminished TNF-α-induced IκB-α degradation and subsequent nuclear translocation of NF-κB p65 in ECs. In the animal study, resveratrol supplementation in diet significantly diminished TNF-α-induced increases in circulating levels of adhesion molecules and cytokines, monocyte adhesion to mouse aortic ECs, F4/80-positive macrophages and VCAM-1 expression in mice aortas and restored the disruption in aortic elastin fiber caused by TNF-α treatment. The animal study also confirmed that resveratrol blocks the activation of NF-κB In Vivo. In conclusion, resveratrol at physiologically achievable concentrations displayed protective effects against TNF-α-induced vascular endothelial inflammation in vitro and In Vivo. The ability of resveratrol in reducing inflammation may be associated with its role as a down-regulator of the NF-κB pathway.
Highlights
Cardiovascular disease (CVD) is the number one cause of death in the United States and one of the top leading causes of death worldwide, mostly due to the westernization of traditional diets [1,2,3]
We demonstrated that resveratrol at physiologically achievable concentrations (
Clinical studies revealed that free and conjugated forms of resveratrol were present in plasma and urine samples of human subjects who orally consumed resveratrol [32,33], but only up to 2.4 μm of resveratrol was found in the plasma of human participants who orally ingested a high dose of resveratrol (5 g) [33]
Summary
Cardiovascular disease (CVD) is the number one cause of death in the United States and one of the top leading causes of death worldwide, mostly due to the westernization of traditional diets [1,2,3]. Accumulating evidence suggests that these processes are driven by proinflammatory chemokines, such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) [6,10,11]. It is well-established that tumor necrosis factor-alpha (TNF-α), a major pleiotropic proinflammatory cytokine, plays a pivotal role in endothelial dysfunction and subsequent damage to vascular function [12,13]. Since inflammation-driven endothelial dysfunction is a prime trigger in atherosclerosis initiation and exacerbation, compounds that attenuate TNF-α- induced NF-κB activation and subsequent expression of inflammatory markers are potential therapies to vascular endothelial dysfunction
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