Red Wine Does Not Reduce Mature Atherosclerosis in Apolipoprotein E–Deficient Mice

Bentzon, Jacob Fog; Skovenborg, Erik; Hansen, Carsten Palnæs; Møller, Jan; Gaulejac, N. Saint-Cricq De; Proch, John; Falk, Erling

doi:10.1161/01.cir.103.12.1681

Cited by 59 publications

(37 citation statements)

References 31 publications

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“…20 However, not all antioxidants are protective, and supplementing the diet with either red wine polyphenol or ethanol had no effect. 21 Furthermore, probucol paradoxically increased atherosclerosis in Apoe Ϫ/Ϫ mice, 22 raising a caution that antioxidants can also be strong oxidants in some circumstances. 23 Our results show that vitamin C is not a key player in the early steps of atherogenesis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid

Nakata

Maeda

2002

Circulation

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Background-Oxidative stress is thought to play an important role in atherogenesis, suggesting that antioxidants could prevent coronary artery disease. However, the efficacy of vitamin C in reducing atherosclerosis is debatable in humans and has not been tested rigorously in animals. Methods and Results-GuloϪ/Ϫ Apoe Ϫ/Ϫ mice were used to test a hypothesis that chronic vitamin C deficiency enhances the initiation and development of atherosclerosis. These mice are dependent on dietary vitamin C because of the lack of L-gulonolactone-␥-oxidase and are prone to develop atherosclerosis because of lacking apolipoprotein E. Beginning at 6 weeks of age, the Gulo Ϫ/Ϫ Apoe Ϫ/Ϫ mice were fed regular chow or Western-type diets containing high fat and supplemented with either 0.033 g or 3.3 g/L of vitamin C in their drinking water. This regimen produced mice with chronically low vitamin C (average 1.5 g/mL in plasma) or high vitamin C (average 10 to 30 g/mL in plasma). Morphometric analysis showed that within each sex, age, and diet group, the sizes of the atherosclerotic plaques were not different between low vitamin C mice and high vitamin C mice. However, advanced plaques in the low vitamin C mice had significantly reduced amounts of Sirius red-staining collagen (36.4Ϯ2.2% versus 54.8Ϯ2.3%, PϽ0.0001), larger necrotic cores within the plaques, and reduced fibroproliferation and neovascularization in the aortic adventitia. Conclusions-Chronic vitamin C deficiency does not influence the initiation or progression of atherosclerotic plaques but severely compromises collagen deposition and induces a type of plaque morphology that is potentially vulnerable to rupture.

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Section: Discussionmentioning

confidence: 99%

Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid

Nakata

Maeda

2002

Circulation

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“…The aortic root was sectioned serially at 4-m intervals from the cardiac end (24). Once the aortic sinuses appeared, every other section was collected on glass slides.…”

Section: Analysis Of Aortic Atherosclerosismentioning

confidence: 99%

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Bro

Bentzon²,

Falk³

et al. 2003

Journal of the American Society of Nephrology

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140

116

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Abstract. Cardiovascular mortality is 10 to 20 times increased in patients with chronic renal failure (CRF). Risk factors for atherosclerosis are abundant in patients with CRF. However, the pathogenesis of cardiovascular disease in CRF remains to be elucidated. The effect of CRF on the development of atherosclerosis in apolipoprotein E-deficient male mice was examined. Seven-week-old mice underwent 5/6 nephrectomy (CRF, n ϭ 28), unilateral nephrectomy (UNX, n ϭ 24), or no surgery (n ϭ 23). Twenty-two weeks later, CRF mice showed increased aortic plaque area fraction (0.266 Ϯ 0.033 versus 0.045 Ϯ 0.006; P Ͻ 0.001), aortic cholesterol content (535 Ϯ 62 versus 100 Ϯ 9 nmol/cm 2 intimal surface area; P Ͻ 0.001), and aortic root plaque area (205,296 Ϯ 22,098 versus 143,662 Ϯ 13,302 m 2 ; P Ͻ 0.05) as compared with no-surgery mice; UNX mice showed intermediate values. The plaques from uremic mice contained CD11b-positive macrophages and showed strong staining for nitrotyrosine. Systolic BP and plasma homocysteine concentrations were similar in uremic and nonuremic mice. Plasma urea and cholesterol concentrations were elevated 2.6-fold (P Ͻ 0.001) and 1.5-fold (P Ͻ 0.001) in CRF compared with no-surgery mice. Both variables correlated with aortic plaque area fraction (r 2 ϭ 0.5, P Ͻ 0.001 and r 2 ϭ 0.3, P Ͻ 0.001, respectively) and with each other (r 2 ϭ 0.5, P Ͻ 0.001). On multiple linear regression analysis, only plasma urea was a significant predictor of aortic plaque area fraction. In conclusion, the present findings suggest that uremia markedly accelerates atherogenesis in apolipoprotein E-deficient mice. This effect could not be fully explained by changes in BP, plasma homocysteine levels, or total plasma cholesterol concentrations. Thus, the CRF apolipoprotein E-deficient mouse is a new model for studying the pathogenesis of accelerated atherosclerosis in uremia.

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“…Some in vivo studies in rabbits (22, 116), hamsters (105), and mice (45) suggest that the antioxidant properties of wine limit early atherosclerotic plaque formation and progression. However, a reduction in mature atherosclerosis in Apo-E-deficient mice was not observed with red wine treatment, although Ͻ60% of these treated mice had measurable blood ethanol levels (9). Human studies suggest that the consumption of red wine (62) or alcohol-free red wine (89) leads to a significant increase in serum antioxidant activity, which may reduce the susceptibility of LDL to oxidation in vivo (70), limiting the extent of atheroma formation.…”

Section: Impairment Of Plaque Initiation and Progressionmentioning

confidence: 99%

Antiatherogenic potential of red wine: clinician update

Szmitko¹,

Verma²

2005

American Journal of Physiology-Heart and Circulatory Physiology

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Complications of atherosclerosis remain the leading cause of morbidity and mortality in industrialized countries. Epidemiological studies have repeatedly demonstrated that moderate alcohol intake has a beneficial effect on cardiovascular disease. The purpose of this review is to examine the epidemiological and biological evidence supporting the intake of red wine as a means of reducing atherosclerosis. On the basis of epidemiological studies, moderate intake of alcoholic beverages, including red wine, reduces the risk of cardiovascular, cerebrovascular, and peripheral vascular disease in populations. In addition to the favorable biological effects of alcohol on the lipid profile, on hemostatic factors, and in reducing insulin resistance, the phenolic compounds in red wine appear to interfere with the molecular processes underlying the initiation, progression, and rupture of atherosclerotic plaques. Whether red wine is more beneficial than other types of alcohol remains unclear. Definitive data from a large-scale, randomized clinical end-point trial of red wine intake would be required before physicians can advise patients to use wine as part of preventative or medical therapies.

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Red Wine Does Not Reduce Mature Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract: Neither ethanol nor red wine polyphenols reduced mature atherosclerosis or changed the content of collagen in plaques in apolipoprotein E-deficient mice.

Cited by 59 publications

References 31 publications

Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid

Vulnerable Atherosclerotic Plaque Morphology in Apolipoprotein E–Deficient Mice Unable to Make Ascorbic Acid

Chronic Renal Failure Accelerates Atherogenesis in Apolipoprotein E–Deficient Mice

Antiatherogenic potential of red wine: clinician update

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