Wine constituents inhibit thrombosis but not atherogenesis in C57BL/6 apolipoprotein E-deficient mice (original) (raw)
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Annals of the New York Academy of Sciences, 2002
Epidemiological studies have suggested that cardiovascular disease can be decreased by moderate wine consumption, but an overall quantitative estimation of the relationship between wine intake and vascular risk is lacking. A meta-analysis was therefore performed on 19 studies selected on the basis of the availability of specific information on the cardiovascular relative risk (RR) associated with wine consumption. A significant risk reduction (RR: 0.66, 95% CI 0.57-0.75) was associated with moderate (1-2 drinks or 150-300 mL/d) versus no wine consumption. In five studies which excluded ex-drinkers as reference group, the overall RR associated with wine consumption was 0.61 (95% CI 0.57-0.75). A dose-response relation between wine intake and vascular risk resulted in a J-shaped curve, with a significant risk reduction at about 300 mL/d (trend analysis p = 0.032). Two studies were also performed to investigate the effects of wine polyphenols on experimental thrombosis in rats. Supplem...
Journal of Thrombosis and Haemostasis, 2005
The concept of the 'French paradox' has been recently challenged. As it is difficult in a short period to produce direct clinical evidence of the protective effect of red wine on thrombosis, we evaluated such a possibility in an experimental model mimicking the conditions of the 'French paradox'. Normolipidemic rats (FNL) were fed a standard diet or a 2% cholesterol-rich-diet (Ch-rich-diet) for 5 months: the latter was given either alone (FNL + D) or in combination with 'alcohol-free' red wine (FNL + D + 5 W). Arterial thrombosis was measured as the occlusion time (OT) of an artificial prosthesis inserted into the abdominal aorta. Lipid levels, platelet adhesion to fibrillar collagen, factor VII (FVII) clotting activity and fibrinogen levels were also measured. Compared to animals fed a standard diet, Ch-rich diet induced in FNL rats a several-fold increase in lipids and FVII levels with a concomitant significant increase in both thrombotic tendency (shortening of the OT) and platelet adhesion. 'Alcohol-free' red wine supplementation almost completely reverted the prothrombotic effect of the Ch-rich-diet. Indeed, the OT was prolonged from 78 +/- 3 to 122 +/- 10 h (P < 0.01), while platelet adhesion to fibrillar collagen was reduced from 49 +/- 3.5% to 30 +/- 2.8%. Neither the increase in lipid levels induced by Ch-rich diet nor FVII or fibrinogen levels were modified by wine supplementation. In conclusion, in experimental animals, this study supports the concept of the 'French paradox' that regular consumption of wine (rather than alcohol) was able to prevent arterial thrombosis associated with dietary-induced hypercholesterolemia, an effect mediated by downregulation of platelet function.
The effect of red wine on experimental atherosclerosis:lipid-independent protection
Experimental and Molecular Pathology, 1999
To assess the effect of red wine on atherosclerosis, New Zealand rabbits were given 1% cholesterol diet for 12 weeks and compared to animals that received the diet plus either red wine or nonalcoholic wine products (NAWP). Diet induced marked increases in total and LDL cholesterol; yet no significant changes in HDL and triglyceride concentrations occurred. In the control group, plaque area was 69 +-9% of the aortic surface, while in the wine and NAWP groups it was only 38 _+ 9 and 47 -+ 12%, respectively (P < 0.0001). The average intima/media thickness ratio was 0.60 __ 0.2 in control animals, 0.14 ~ 0.09 in the wine group, and 0.39 -+ 0.19 in the NAWP group (P < 0.0001). No significant differences were noted in LDL oxidizability among treatments. Thus, both red wine and NAWP can prevent plaque formation in hypercholesterolemic rabbits despite significant increases in LDL. We speculate that anti-platelet effect, blockade of expression of endothelial cell adhesion molecules, and/or NO stimulation by red wine flavonoids are possible explanations.
British Journal of Pharmacology, 1999
The effects of ethyl alcohol and wine (red and white) on haemostatic parameters and experimental thrombosis were studied in rats; NO was evaluated as a possible mediator of these effects.We found that red wine (12% alcohol) supplementation (8.4±0.4 ml d−1 in drinking water, for 10 days) induced a marked prolongation of ‘template’ bleeding time (BT) (258±13 vs 132±13 s in controls; P<0.001), a decrease in platelet adhesion to fibrillar collagen (11.6±1.0 vs 32.2±1.3%; P<0.01) and a reduction in thrombus weight (1.45±0.33 vs 3.27±0.39 mg; P<0.01).Alcohol-free red wine showed an effect similar to red wine. In contrast, neither ethyl alcohol (12%) nor white wine (12% alcohol) affected these systems.All these effects were also observed after red wine i.v. injection (1 ml kg−1 of 1 : 4 dilution) 15 min before the experiments.The effects of red wine were prevented by the NO inhibitor, Nωnitro-L-arginine-methyl ester (L-NAME). L-arginine, not D-arginine, reversed the effect of L-NAME on red wine infusion.Red wine injection induced a 3 fold increase in total radical-trapping antioxidant parameter values of rat plasma with respect to controls, while white wine and alcohol did not show any effect.Our study provides evidence that red wine modulates primary haemostasis and prevents experimental thrombosis in rats, independently of its alcohol content, by a NO-mediated mechanism.The effects of ethyl alcohol and wine (red and white) on haemostatic parameters and experimental thrombosis were studied in rats; NO was evaluated as a possible mediator of these effects.We found that red wine (12% alcohol) supplementation (8.4±0.4 ml d−1 in drinking water, for 10 days) induced a marked prolongation of ‘template’ bleeding time (BT) (258±13 vs 132±13 s in controls; P<0.001), a decrease in platelet adhesion to fibrillar collagen (11.6±1.0 vs 32.2±1.3%; P<0.01) and a reduction in thrombus weight (1.45±0.33 vs 3.27±0.39 mg; P<0.01).Alcohol-free red wine showed an effect similar to red wine. In contrast, neither ethyl alcohol (12%) nor white wine (12% alcohol) affected these systems.All these effects were also observed after red wine i.v. injection (1 ml kg−1 of 1 : 4 dilution) 15 min before the experiments.The effects of red wine were prevented by the NO inhibitor, Nωnitro-L-arginine-methyl ester (L-NAME). L-arginine, not D-arginine, reversed the effect of L-NAME on red wine infusion.Red wine injection induced a 3 fold increase in total radical-trapping antioxidant parameter values of rat plasma with respect to controls, while white wine and alcohol did not show any effect.Our study provides evidence that red wine modulates primary haemostasis and prevents experimental thrombosis in rats, independently of its alcohol content, by a NO-mediated mechanism.British Journal of Pharmacology (1999) 127, 747–755; doi:10.1038/sj.bjp.0702586
Arteriosclerosis, Thrombosis, and Vascular Biology, 1997
Epidemiological and experimental studies suggest that circulating erythrocytes play a role in the incidence of coronary heart disease. We investigated the influence of phenylhydrazine (PHZ)-induced anemia on the formation of atherosclerotic lesions in apo E-deficient mice on regular chow and on a high-fat, high-cholesterol diet during 10 weeks. The repeated doses of PHZ caused sustained anemia throughout the study, changes in the physical characteristics of erythrocytes and increased retyculocyte count. The lesions of the anemic animals were smaller than in the controls and this was even more evident in mice fed with the atherogenic diet. A positive correlation was found between circulating red blood cells at the end of the experiment and the area of aortic lesion. There was also a negative association between the lesion and the retyculocyte count. This reduced progression of atherosclerotic lesions is independent of nutritional status or the lipoprotein cholesterol distribution. The results suggest that mechanisms related to the number of circulating red blood cells may have a significant influence on the development of atherosclerosis.
Moderate consumption of red wine and human platelet responsiveness
Thrombosis Research, 2011
Available studies showed an inverse association between red wine consumption and prevalence of vascular risk factors in coronary hearth disease and stroke. Effects were mainly associated to wine antioxidant and antiaggregant properties. Actually, in vitro studies indicate a favourable effect of wine and/or of its non-alcoholic components in decreasing platelet sensitivity and aggregability. In a 4-week supplementation in 15 healthy male volunteers, we evaluated whether moderate red wine consumption might improve antioxidant defence mechanisms and promote positive modulation of inflammatory cytokines and cell adhesion molecules in relation to platelet responsiveness. We did not find any change of ADP-and collagen-induced platelet aggregation ex vivo, any change of biomarkers of oxidative stress, and any change of plasma lipid profile and haemostatic parameters, with the only exception of decreased fibrinogen levels (Pb 0.05). We also found an increase of mean platelet volume (Pb 0.05) without any significant modification of CD40 Ligand and P-selectin levels. Increased expressions of intercellular adhesion molecule-1, soluble E-selectin and interleukin-6 (P b 0.05) were also observed. According to our findings increased circulating levels of inflammatory and endothelial cell activation markers may indicate a low-grade systemic inflammation and vascular activation that could be responsible for the lack of inhibition or of decreased platelet responsiveness, possibly because the plasmatic increase of wine antioxidant compounds is insufficient to improve endothelial function and to counteract the influence of ethanol on endothelial activation.
Antithrombotic Effect of Polyphenols in Experimental Models
Annals of the New York Academy of Sciences, 2002
Epidemiological studies have suggested that cardiovascular disease can be decreased by moderate wine consumption, but an overall quantitative estimation of the relationship between wine intake and vascular risk is lacking. A meta-analysis was therefore performed on 19 studies selected on the basis of the availability of specific information on the cardiovascular relative risk (RR) associated with wine consumption. A significant risk reduction (RR: 0.66, 95% CI 0.57-0.75) was associated with moderate (1-2 drinks or 150-300 mL/d) versus no wine consumption. In five studies which excluded ex-drinkers as reference group, the overall RR associated with wine consumption was 0.61 (95% CI 0.57-0.75). A dose-response relation between wine intake and vascular risk resulted in a J-shaped curve, with a significant risk reduction at about 300 mL/d (trend analysis p = 0.032). Two studies were also performed to investigate the effects of wine polyphenols on experimental thrombosis in rats. Supplementation for 10 days with alcohol-free red wine--but not white wine or alcohol--induced a significant reduction of stasis-induced venous thrombosis, an effect blunted by NO synthase inhibitor L-NAME. In rats with diet-induced hyperlipidemia, alcohol-free red wine supplementation significantly delayed the thrombotic occlusion of an artificial prosthesis inserted into the abdominal aorta, but did not affect the increased cholesterol and triglyceride levels. TRAP values were significantly higher in animals receiving alcohol-free wine. Altogether these experimental data support an antithrombotic role of polyphenols in the reduced vascular risk associated with moderate wine consumption in man, as shown by our epidemiological studies.
Cardioprotective effects of red wine and vodka in a model of endothelial dysfunction
Journal of Surgical Research, 2012
Background: Moderate alcohol consumption is largely believed to be cardioprotective, while red wine is hypothesized to offer benefit in part due to the proangiogenic and antioxidant properties of polyphenols. We investigated the cardiovascular effects of both red wine and vodka in a swine model of endothelial dysfunction. Methods: Twenty-seven male Yorkshire swine fed a high-fat/cholesterol diet were divided into three groups and received either no alcohol (Control), red wine, or vodka. After 7 wk, myocardial perfusion was measured, and ventricular tissue was analyzed for microvascular reactivity and immunohistochemical studies. Results: There were no differences in myocardial perfusion, in arteriolar or capillary density, or in VEGF expression among groups. Total protein oxidation as well as expression of superoxide dismutase-1 and-2 and NADPH oxidase was decreased in both treatment groups compared to controls. Endothelium-dependent microvessel relaxation, however, was significantly improved only in the red wineesupplemented group. Conclusions: Supplementation with both red wine and vodka decreased oxidative stress by several measures, implicating the effects of ethanol in reducing oxidative stress in the myocardium. However, it was only in the red wineesupplemented group that an improvement in microvessel function was observed. This suggests that a component of red wine, independent of ethanol, possibly a polyphenol such as resveratrol, may confer cardioprotection by normalizing endothelial dysfunction induced by an atherogenic diet.
The Mediterranean Lecture: Wine and Thrombosis – From Epidemiology to Physiology and Back
Pathophysiology of Haemostasis and Thrombosis, 2003
The protective effect of moderate alcohol consumption on the risk of cardiovascular disease has been consistently shown in many epidemiological studies. Antiatherogenic alterations in plasma lipoproteins, particularly increase in high-density lipoprotein (HDL) cholesterol, are considered as the most plausible mechanism of the protective effect of alcohol consumption on coronary artery disease (CHD). Other potential mechanisms contributing to the cardio-protective effects of moderate alcohol consumption include anti-thrombotic down regulation of blood platelet function, as well as of the coagulation and fibrinolysis balance. Since the proposal of a "French paradox" in the early Nineties, the possibility that consuming alcohol in the form of wine might confer a protection against CHD above that expected from its alcohol content, has made the topic "wine and health" increasingly popular. Many epidemiological studies have explored such a possibility, by comparing specific alcoholic beverage types (wine, beer, liqueur) in respect to their relative capacity to reduce the risk of CHD. In parallel, experimental stud