Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

Differential modulation of oxidative and nitrosative stress pathways by red wine polyphenols, ProvinolsTM, in tissues from Zucker fatty rats (fa/fa).

Date du colloque : 2009National audienc

Provinols™ improve endothelial function in ZF rats.

<p>Acetylcholine (Ach)-induced relaxation in rat aorta (A), small mesenteric arteries (SMA) (B), SMA in the presence of inhibitors of EDHF and COX components (C) (apamine, APA; charybdotoxin, CTX; indomethacin, INDO), SMA in the presence of inhibitors of NO and COX components (D) (INDO, L-NAME). Results are expressed as a percentage of relaxation. Values are means±SEM (<i>n</i> = 6). *<i>P</i><0.05, ***<i>P</i><0.001 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05, ###<i>P</i><0.001 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p

Provinols™ improve metabolic parameters in ZF rats.

<p>Circulating levels of glucose (A), fructosamine (B), total cholesterol (C), ratio between LDL- and HDL-cholesterol (D), triglygerides (E), creatinin (F) and uric acid (G) were evaluated in fasting plasma of rats. Values are means±SEM (<i>n</i> = 11–12). *<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05, ###<i>P</i><0.001 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p

Provinols™ reduce O₂⁻ vascular release in vessels from ZF rats.

<p>O₂⁻ production in aorta (A), carotid arteries (B) and small mesenteric arteries (C) from Zucker fatty (ZF) and ZF+Provinols™ rats. Values are expressed as units of amplitude (A)/mg weight of dried tissue (dw). Western blots revealing expression of Nox-1 (D), Nox-2 (E), Nox-4 (F), Mn-SOD (G), Cu/Zn-SOD (H) and Ec-SOD (I) in aorta expressed as arbitrary units (A.U.). (<i>n</i> = 6). *<i>P</i><0.05, **<i>P</i><0.01 <i>vs.</i> ZF rats.</p

Provinols™ increase NO vascular release in vessels from ZF rats.

<p>NO production in aorta (A), carotid arteries (B) and small mesenteric arteries (C) from Zucker fatty (ZF) and ZF+Provinols™ rats. Values are expressed as units of amplitude (A)/mg weight of dried tissue (dw). Western blots revealing expression of eNOS (D), phosphorylation of eNOS at Thr495 (E), and NOS Ser1177 (F) and expression of caveolin-1 (G) in aorta expressed as arbitrary units (A.U.). (<i>n</i> = 6). *<i>P</i><0.05, **<i>P</i><0.01 <i>vs.</i> ZF rats.</p

Provinols™ improve cardiac function in ZF rats.

<p>Echocardiography measurements of diastolic left ventricular dimension (LVDd), systolic left ventricular dimension (LVDs), cardiac output and fraction of ejection (A–D). Systolic blood pressure was evaluated using tail-cuff technique (E). Total arterial peripheral resistances were calculated from blood pressure and cardiac output (F). Values are means±SEM (<i>n</i> = 6). *<i>P</i><0.05 Zucker fatty (ZF) rats <i>vs.</i> lean rats; #<i>P</i><0.05 ZF+Provinols™ rats <i>vs.</i> ZF rats.</p

Endothelial Dysfunction Caused by Circulating Microparticles from Patients with Metabolic Syndrome

Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O2− was linked to both reduced expression of p47phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction