Effect of Low Doses of Red Wine and Pure Resveratrol on Circulating Endothelial Progenitor Cells

Abstract

Circulating endothelial progenitor cells (EPCs) play a significant role in neovascularization of ischaemic tissues and in re-endothelization of injured blood vessels. Identification of compounds able to enhance EPC levels and improve their functional activity, noticeably compromised by risk factors for coronary heart disease, is of clinical interest. This study evaluates the effects of red wine on EPCs. After being isolated from total peripheral blood mononuclear cells, EPC phenotype was confirmed by the presence of double positive cells for DiLDL uptake and lectin binding and by expression of CD34, CD133 and VE-cadherin cell surface markers. Long-term culture in the presence of red wine (1 microl/ml), containing resveratrol (Resv) at physiological concentration (nM), determined a time-dependent amelioration of cell number (P < 0.05). The presence of red wine prevented the TNF-alpha-induced reduction of EPC number (P < 0.05) and this effect was accompanied by reduced p38-phosphorylation expression levels (P < 0.05) and increased NOx levels (P < 0.05) Indeed, pure Resv alone significantly improved the TNF-alpha reduced EPC number (P < 0.05). This evidence indicates novel beneficial effects of red wine and Resv in the positive modulation of EPCs levels.

Intake of Red Wine Increases the Number and Functional Capacity of Circulating Endothelial Progenitor Cells by Enhancing Nitric Oxide Bioavailability

“…28 Furthermore, RW improved ischemia-induced neovascularization in hypercholesterolemic apolipoprotein E-deficient mice after hindlimb ischemia by increasing the number and functional activity of EPC. 29 Balestrieri et al 30 reported that low doses of RW in vitro upregulated the number of circulating EPC during treatment with TNF-␣. However, the relationship between RW consumption and circulating EPC remains unclear in humans.…”

Critical Role of the Nitric Oxide/Reactive Oxygen Species Balance in Endothelial Progenitor Dysfunction

“…6). Resveratrol also attenuates tumor necrosis factor-alpha-induced EPC senescence and improves EPC function, including tube formation in vitro (8,41). The increase of telomerase activity in EPCs might also contribute significantly to the reduced senescence of EPC by resveratrol treatment (131).…”

“…Resveratrol is a known stimulator of sirtuin-1 (Sirt1), which in turn promotes angiogenesis (68). Indeed, SIRT1 is a critical modulator of EPCs dysfunction (8) and knockdown of Sirt1 by siRNA results in diminished EPC angiogenesis and increased senescence (136). Thus, activation of SIRT1 by resveratrol may contribute to the vasoprotective and angiogenic effects of this compound.…”

Emerging roles of SIRT1 in vascular endothelial homeostasis

“…As such, resveratrol was recently shown to increase the number of endothelial progenitor cells in vitro. [78][79][80] The finding that SIRT1 acts as an important regulator of postnatal vascular growth suggests that strategies to inhibit SIRT1 activity could also provide an opportunity for anti-angiogenesis therapies. Dysregulation of angiogenic growth has been shown to contribute to numerous pathologies including malignant or inflammatory disorders and anti-angiogenic agents such as α-VEGF have been shown to prolong the survival of cancer patients.…”