Resveratrol mediates anti-atherogenic effects on cholesterol flux in human macrophages and endothelium via PPARγ and adenosine

Voloshyna, Iryna; Hai, Ofek; Littlefield, Michael J.; Carsons, Steven E.; Reiss, Allison B.

doi:10.1016/j.ejphar.2012.08.024

Cited by 107 publications

(90 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Different studies have shown a modulation of the expression of cholesterol metabolism-related genes, such as abca1, abcg1 and srb1, in macrophages responding to treatment with polyphenols quercetin, resveratrol and extra virgin olive oil, another source of polyphenols (Voloshyna et al 2013;Lee et al 2013;Helal et al 2013). However, in our study, of all the analysed genes that are involved in cholesterol homoeostasis, only lss was up-regulated in PBMCs in response to the administration of GSPE in the STD-GSPE animals.…”

Section: Discussioncontrasting

confidence: 53%

The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

et al. 2014

View full text Add to dashboard Cite

We previously demonstrated that hamsters that were fed either a standard diet (STD) or a high-fat diet (HFD) and treated with a grape seed procyanidin extract (GSPE) showed decreased adiposity and circulating levels of free fatty acids compared with hamsters treated with a vehicle (Caimari et al. in Int J Obes 37:576-83, 2013, doi:10.1038/ijo.2012). Here, we tested whether the gene expression changes in peripheral blood mononuclear cells (PBMCs) can reflect these metabolic effects and the dyslipidaemia produced by the HFD feeding in the same cohort of animals. The mRNA levels of a subset of genes were also studied in the liver in order to evaluate the capacity of PBMCs to reflect the metabolic adaptations that occur in this organ. In PBMCs, we reported a simultaneous up-regulation of the lipid-related genes involved in both the anabolic (pparc, acc1 and gpat) and the catabolic (ppara, ucp2, atgl and hsl) pathways in response to the GSPE treatment, similar but no identical to previous observations in retroperitoneal white adipose tissues of these animals. Furthermore, the key cholesterol metabolism genes srebp2 and ldlr were significantly down-regulated in PBMCs of both HFD-fed groups compared with the STD groups. Although the expression of srebp2 in the liver followed a similar pattern to that obtained in PBMCs, no comparable changes were found between the liver and PBMCs in the expression of most of the studied genes. In conclusion, our results highlight the potential of PBMCs as a high accessible tissue for the indirect study of cholesterol and adipose tissue metabolism dynamics.

show abstract

Section: Discussioncontrasting

confidence: 53%

The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

et al. 2014

View full text Add to dashboard Cite

show abstract

“…One candidate for use in controlling cholesterol outflow is resveratrol (3,5,4 0 -trihydroxy-trans-stilbene), a bioactive molecule used in dietary supplements, already reported to display cardioprotective and anti-inflammatory properties. 13,14 Here we present additional data to support the use of resveratrol in blocking atheroma-promoting effects of the lupus milieu in humans and in a murine model. We report that resveratrol can protect THP-1 human macrophages from pro-atherogenic effects of SLE plasma.…”

Section: Introductionmentioning

confidence: 90%

Resveratrol counters systemic lupus erythematosus-associated atherogenicity by normalizing cholesterol efflux

Voloshyna

Teboul

Littlefield

et al. 2016

Exp Biol Med (Maywood)

Self Cite

View full text Add to dashboard Cite

Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Numerous investigations by our group and others have indicated cardioprotective and anti-inflammatory properties of resveratrol. The present study explored potential atheroprotective actions of resveratrol on cholesterol efflux in cultured human macrophages exposed to plasma from systemic lupus erythematosus (SLE) patients. These results were confirmed in ApoEknockout mice, displaying a lupus profile with accelerated atherosclerosis. Resveratrol treatment attenuated atherosclerosis in these mice. THP-1 human macrophages were exposed to 10% pooled or individual plasma from patients who met diagnostic criteria for SLE. Expression of multiple proteins involved in reverse cholesterol transport (ABCA1, ABCG1, SR-B1, and cytochrome P450 27-hydroxylase) was assessed using QRT-PCR and Western blotting techniques. Ten-week-old ApoE(n ¼ 30) were randomly divided into two equal groups of 15, one of which received 0.01% resveratrol for 10 consecutive weeks. Atherosclerosis progression was evaluated in murine aortas. Bone marrow-derived macrophages (BMDM) were cultured and expression of cholesterol efflux proteins was analyzed in each group of mice. Our data indicate that inhibition of cholesterol efflux by lupus plasma in THP-1 human macrophages is rescued by resveratrol. Similarly, administration of resveratrol in a lupus-like murine model reduces plaque formation in vivo and augments cholesterol efflux in BMDM. This study presents evidence for a beneficial role of resveratrol in atherosclerosis in the specific setting of SLE. Therefore, resveratrol may merit investigation as an additional resource available to reduce lipid deposition and atherosclerosis in humans, especially in such vulnerable populations as lupus patients.

show abstract

“…However the potential side effects of long term IFN-γ inhibition still needs to be assessed. or serine 727 as well as JAK2 activation in human macrophages in vitro [47] . These compounds represent promising avenues for therapies targeted at the downstream signaling events in the JAK-STAT pathway in order to reduce the pro-inflammatory effects of IFN-γ.…”

Section: Resultsmentioning

confidence: 99%

Interferon-γ: Promising therapeutic target in atherosclerosis

Moss

Ramji

2015

WJGEM

View full text Add to dashboard Cite

Atherosclerosis is a chronic inflammatory disorder of the vasculature and is the primary cause of cardiovascular disease (CVD). CVD is currently the world's leading cause of death and the numbers are predicted to rise further because of a global increase in risk factors such as diabetes and obesity. Current therapies such as statins have had a major impact in reducing mortality from CVD. However, there is a marked residual CVD risk in patients on statin therapy. It is therefore important to understand the molecular basis of this disease in detail and to develop alternative novel therapeutics. Interferon-γ (IFN-γ) is a pro-inflammatory cytokine that is often regarded as a master regulator of atherosclerosis development. IFN-γ is able to influence several key steps during atherosclerosis development, including pro-inflammatory gene expression, the recruitment of monocytes from the blood to the activated arterial endothelium and plaque stability. This central role of IFN-γ makes it a promising therapeutic target. The purpose of this editorial is to describe the key role IFN-γ plays during atherosclerosis development, as well as discuss potential strategies to target it therapeutically.

show abstract

Resveratrol mediates anti-atherogenic effects on cholesterol flux in human macrophages and endothelium via PPARγ and adenosine

Cited by 107 publications

References 51 publications

The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

The intake of a high-fat diet and grape seed procyanidins induces gene expression changes in peripheral blood mononuclear cells of hamsters: capturing alterations in lipid and cholesterol metabolisms

Resveratrol counters systemic lupus erythematosus-associated atherogenicity by normalizing cholesterol efflux

Interferon-γ: Promising therapeutic target in atherosclerosis

Contact Info

Product

Resources

About