Antioxidant Intervention Prevents Renal Neovascularization in Hypercholesterolemic Pigs

Chade, Alejandro; Bentley, Michael D.; Zhu, Xiangyang; Rodriguez-Porcel, Martin; Niemeyer, Sara; Amores-Arriaga, Beatriz; Napoli, Claudio; Ritman, Erik L.; Lerman, Amir; Lerman, Lilach O.

doi:10.1097/01.asn.0000130428.85603.6b

Cited by 68 publications

(101 citation statements)

References 51 publications

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“…Twelve female domestic crossbred pigs (50 -60 kg) were randomized to receive a normal diet without (n ϭ 6) or with antioxidant vitamin supplementation (1 g/day vitamin C, 100 IU ⅐ kg Ϫ1 ⅐ day Ϫ1 vitamin E; vitamin supplemented, n ϭ 6) for 12 wk. Our group has previously shown that during increased oxidative stress associated with hypercholesterolemia or hypertension, this regimen is effective in restoring redox balance, decreasing neovascularization, and improving renal and myocardial vascular function (5,44,54,55).…”

Section: In Vivo Studymentioning

confidence: 99%

“…Interestingly, chronic antioxidant vitamin supplementation in hypercholesterolemia blunted renal neovascularization, in association with a decrease in oxidative stress and renal damage (5). However, the effects of such a regimen of antioxidant vitamins on the microvascular architecture of the normal kidney, or the associated mechanisms, remain unknown.…”

mentioning

confidence: 99%

“…In the kidney, exposure to cardiovascular risk factors such as hypercholesterolemia increases tissue oxidative stress, impairs vascular endothelial and renal function (7) and induces renal neovascularization, which is most pronounced in the renal cortex (2,5). Interestingly, chronic antioxidant vitamin supplementation in hypercholesterolemia blunted renal neovascularization, in association with a decrease in oxidative stress and renal damage (5).…”

mentioning

confidence: 99%

“…However, excessive formation of new vessels has been associated with several pathological conditions, such as cancer (3,10), inflammation (5), and atherosclerosis (20,25), and has been shown to participate in disease progression (49). Interestingly, these conditions are all characterized by disequilibrium in redox status with increased production of reactive oxygen species (ROS).…”

mentioning

confidence: 99%

“…Accordingly, previous human and animal studies have demonstrated that chronic supplementation with antioxidant vitamins E and C in cancer or in the presence of cardiovascular risk factors confers an antiangiogenic effect, resulting in decreased tumor mass growth (41) and improvement in vascular and organ function (5,6,55). On the other hand, our group and others have demonstrated that under normal conditions, when basal oxidative stress is not increased, antioxidant vitamins can have a paradoxical pro-oxidant effect (21,48) and impair micro-and macrovascular function.…”

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confidence: 99%

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Antioxidant vitamins induce angiogenesis in the normal pig kidney

Daghini

Zhu

Versari

et al. 2007

American Journal of Physiology-Renal Physiology

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The effects of chronic supplementation with antioxidant vitamins on angiogenesis are controversial. The aim of the present study was to evaluate in kidneys of normal pigs the effect of chronic supplementation with vitamins E and C, at doses that are effective in reducing oxidative stress and attenuating angiogenesis under pathological conditions. Domestic pigs were randomized to receive a 12-wk normal diet without ( n = 6) or with antioxidant vitamins supplementation (1g/day vitamin C, 100 IU·kg−1·day−1 vitamin E; n = 6). Electron beam computed tomography (CT) was used to evaluate renal cortical vascular function in vivo, and micro-CT was to assess the spatial density and average diameter of cortical microvessels (diameter <500 μm) ex vivo. Oxidative stress and expressions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1α were evaluated in renal tissue. The effects of increasing concentrations of the same vitamins on redox status and angiogenesis were also evaluated in human umbilical vascular endothelial cells (HUVEC). Compared with normal pigs, the density of cortical transmural microvessels was significantly greater in vitamin-supplemented pigs (149.0 ± 11.7 vs. 333.8 ± 48.1 vessel/cm2, P < 0.05), whereas the cortical perfusion response to ACh was impaired. This was accompanied by a significant increase in tissue oxidative stress and levels of VEGF and HIF-1α. A low dose of antioxidant decreased, whereas a high dose increased, HUVEC oxidative stress and angiogenesis, which was partly mediated by hydrogen peroxide. Antioxidant vitamin supplementation can increase tissue oxidative redox and microvascular proliferation in the normal kidney, probably due to a biphasic effect that depends on basal redox balance.

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Section: In Vivo Studymentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Antioxidant vitamins induce angiogenesis in the normal pig kidney

Daghini

Zhu

Versari

et al. 2007

American Journal of Physiology-Renal Physiology

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Renal Vascular Structure and Rarefaction

Chade¹

2013

Comprehensive Physiology

114

102

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An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation.

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Influence of dietary fat on renal function, lipid profile, sex hormones, and electrolyte balance in rats

Abdel-Rahman

2010

Euro J Lipid Sci & Tech

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Evidence from animal and human studies indicates that abnormal lipid profile may contribute to renal disease progression. The effect of dietary fat level on renal function, electrolyte balance, cholesterol, triacylglycerol, and sex hormones was examined in 54 male and female adult rats. The rats were fed either low/high fat diet (3/20 g/100 g diet) for 12 weeks. In rats fed the high fat diet (HF), the kidney weight/ body weight ratio was significantly increased in comparison with low fat diet (LF). Rats fed the LF diet had significantly lower mean of feed intake and body weight gain percentage compared with both HF and control groups ( p<0.05). HF diets enhanced cholesterol and triacylglycerol significantly in male and female rats, and this increase was associated with a significant increase of testosterone and estradiol levels relative to controls. Uric acid, urea nitrogen and creatinine were increased significantly in HF diet groups for male and female rats. The results indicate that uric acid was increased 100% relative to the control group in male rats when switched to HF diets. In the female group uric acid was increased 35% relative to the control, and for urea nitrogen, 53.4 and 9.6% increase was observed for male and female rats, respectively. Lipid profile in the female group was better than male rats. Significant increase in sodium ions was detected in the serum of male and female rats fed (HF) high fat diets, and the opposite was noticed in potassium ions levels of male and female rats fed HF. Microscopically, examined kidneys of HF diet rats revealed two types of histopathological alterations in both sexes.

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Antioxidant Intervention Prevents Renal Neovascularization in Hypercholesterolemic Pigs

Cited by 68 publications

References 51 publications

Antioxidant vitamins induce angiogenesis in the normal pig kidney

Antioxidant vitamins induce angiogenesis in the normal pig kidney

Renal Vascular Structure and Rarefaction

Influence of dietary fat on renal function, lipid profile, sex hormones, and electrolyte balance in rats

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