Dietary nitrate attenuated endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for NADPH oxidase

Peng, Rou Jun; Luo, Mengjuan; Tian, Rong; Lu, Naihao

doi:10.1016/j.abb.2020.108453

Cited by 14 publications

(25 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our data suggest that even with uninterrupted consumption for more than 1 year, the improvements in vascular reactivity associated with inorganic nitrate are persistent. These effects were mediated by the endothelium and were similar in both sexes, as described earlier in short-term studies [ [46] , [47] , [48] ].…”

Section: Resultssupporting

confidence: 81%

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats

et al. 2021

View full text Add to dashboard Cite

Rationale Dietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxide. Such effects include improvement in cardiovascular, renal and metabolic function, which is partly mediated via reduction of oxidative stress. A recent study even indicates that low dose of dietary nitrite extends life span in fruit flies. Methods In this study, 200 middle-aged Wistar rats of both sexes were supplemented with nitrate or placebo in the drinking water throughout their remaining life and we studied longevity, biochemical markers of disease, vascular reactivity along with careful determination of the cause of death. Results Dietary nitrate did not affect life span or the age-dependent changes in markers of oxidative stress, kidney and liver function, or lipid profile. Ex vivo examination of vascular function, however, showed improvements in endothelial function in rats treated with nitrate. Neoplasms were not more common in the nitrate group. Conclusion We conclude that chronic treatment with dietary nitrate does not affect life span in rats nor does it increase the incidence of cancer. In contrast, vascular function was improved by nitrate, possibly suggesting an increase in health span.

show abstract

Section: Resultssupporting

confidence: 81%

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats

et al. 2021

View full text Add to dashboard Cite

show abstract

“…NO is a major signalling molecule in the human body and has a key role in maintaining vascular tone, smooth muscle cell proliferation, platelet activity and inflammation [46,47]. In animal models, dietary nitrate has been shown to attenuate endothelial dysfunction in animals fed a high-fat diet [48] or with diabetes [49], and has equivalent effects to those of metformin on glucose/insulin homeostasis and even larger effects regarding protection against cardiovascular dysfunction and liver steatosis [50]. We indeed find that nitrate content is also correlated with lower blood cell counts corresponding to lower cardiometabolic risk.…”

Section: Discussionmentioning

confidence: 99%

High intake of vegetables is linked to lower white blood cell profile and the effect is mediated by the gut microbiome

Menni

Louca

Berry

et al. 2021

BMC Med

View full text Add to dashboard Cite

Background Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. Methods Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. Results Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet. Conclusion A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella. Trial registration The ClinicalTrials.gov registration identifier is NCT03479866.

show abstract

“…10 Thus, dietary nitrate might be useful to supply the endothelium with NO and prevent oxidative stress, alongside other measures to control risk factors for atherosclerosis. 11,12,15 Indeed, as we described above, evidence of beneficial effects of long-term dietary nitrate on atherosclerosis has been previously reported from some, but not all studies performed in rats and Apo E À/À mice, [18][19][20] and an association has been observed in epidemiological studies. 21,22 The cohort study by Bondonno et al 21 which included older Australian women aged 70-85 years, and without prevalent atherosclerotic vascular disease and/or diabetes, evaluated the nitrate intake from vegetables.…”

Section: Resultsmentioning

confidence: 60%

“…19 Eight weeks' nitrate supplementation decreased atherosclerotic plaque area and inhibited vascular NADPH oxidase activity and oxidative stress in ApoE À/À mice fed a high fat diet. 20 Epidemiological data suggest that higher vegetable nitrate intake is associated with a lower CIMT and a lower risk of ischaemic cerebrovascular disease events and atherosclerotic vascular disease mortality in 1226 older women, 21,22 and of new cases of cardiovascular disease-related complications over 15-years of follow-up in 5324 middle-aged women. 23 However, direct evidence in humans is scarce, with no randomized-controlled trial data reported to date on whether chronic supplementation with dietary nitrate affects carotid structure and stiffness.…”

mentioning

confidence: 99%

Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure‐independent mechanisms in patients with or at risk of type 2 diabetes mellitus

Morselli

Faconti

Mills

et al. 2021

Brit J Clinical Pharma

View full text Add to dashboard Cite

To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/ doxazosin, to control for blood pressure (BP).Methods: A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate-containing beetroot juice or placebo nitrate-depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3-and 6-months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed-model effect, adjusted for confounders.Results: In total, 93 subjects had a baseline evaluation and 86% had follow-up data.No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate-containing vs. placebo juice significantly lowered CIMT (À0.06 [95% confidence interval À0.12, À0.01], P = .034), an overall difference of $8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (À0.34 [À0.62, À0.06]) however, no difference was detected vs. spironolactone (À0.15 [À0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusions:Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.

show abstract

Dietary nitrate attenuated endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: A critical role for NADPH oxidase

Cited by 14 publications

References 47 publications

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats

High intake of vegetables is linked to lower white blood cell profile and the effect is mediated by the gut microbiome

Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure‐independent mechanisms in patients with or at risk of type 2 diabetes mellitus

Contact Info

Product

Resources

About