Oxidized LDL and NO Synthesis as Biomarkers of Atherogenesis - Correlations with Metabolic Profile in Elderly

Borșa, Claudia; Ionescu, Cristina; Grădinaru, Daniela

doi:10.5772/25686

Cited by 3 publications

(5 citation statements)

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“…Based on the strong interrelationships pointed out in numerous experimental and clinical research (Xu et al, 2013;Ungvari et al, 2012;Wadley et al, 2013;Maiolino et al, 2013a,b;Borsa et al, 2012;Gradinaru et al, 2012Gradinaru et al, , 2013, we summarized the mechanisms of oxidative stress-oxLDL-NO-induced endothelial dysfunction (Fig. 2).…”

Section: Tetyrahydrobiopterinmentioning

confidence: 99%

“…Oxidized LDL and NO exert contradictory actions within the vascular endothelium microenvironment influencing key events in endothelial dysfunction and atherogenesis such as: leukocyte adhesion, platelet aggregation and vascular smooth-muscle cell proliferation and migration. While oxidized LDL (oxLDL) -an oxidative stress biomarker has been identified as a non-traditional, pro-atherogenic emerging risk factor for coronary heart disease, NO is a free radical signal-transducing molecule that maintains the vasodilating tone, modulates in vitro lipid peroxidation reactions and alters pro-inflammatrory gene expression (Holvoet et al,Q4 2008a,b; Borsa et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Oxidized LDL and NO synthesis—Biomarkers of endothelial dysfunction and ageing

Grădinaru

Borșa²,

Ionescu³

et al. 2015

Mechanisms of Ageing and Development

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Oxidized LDL (oxLDL) and nitric oxide (NO) exert contradictory actions within the vascular endothelium microenvironment influencing key events in atherogenesis. OxLDL and NO are so far regarded as representative parameters of oxidative stress and endothelial dysfunction, new targets in prevention, diagnosis and therapy of cardiovascular diseases, and also as candidate biomarkers in evaluating the human biological age. The aim of this review is to explore recent literature on molecular mechanisms and pathophysiological relationships between LDL oxidation, NO synthesis and vascular endothelium function/dysfunction in ageing, focusing on the following aspects: (1) the impact of metabolic status on both LDL oxidation and NO synthesis in relation with oxidative stress, (2) the use of oxidized LDL and NO activity as biomarkers in human studies reporting on cardiovascular outcomes, and (3) evidences supporting the importance of oxidized LDL and NO activity as relevant biomarkers in vascular ageing and age-related diseases.

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Section: Tetyrahydrobiopterinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Oxidized LDL and NO synthesis—Biomarkers of endothelial dysfunction and ageing

Grădinaru

Borșa²,

Ionescu³

et al. 2015

Mechanisms of Ageing and Development

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141

103

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“…As LDL peroxidation and reduced NO synthesis are the two characteristic features of ED, and share significant antagonistic roles in overall vascular health, it may be that any observed benefit of NC on oxLDL may be driven by NOx changes interacting with oxidants on the vascular wall [16]. This speculation requires further study and greater statistical power as the capacity of both bioactive substances as donors of NO may have a direct effect on attenuating the lipid peroxidation reaction [12].…”

Section: Circulatory Biomarkersmentioning

confidence: 99%

“…Thus, in both pathways, nitrite and nitrate act as stable end products that reflect total systemic NO concentrations [10] and their plasma concentrations can be used as surrogate measures of vascular NO bioavailability [4]. Combined measurements of NO metabolic pathway products (nitrate þ nitrite) are termed as NOx [12].…”

Section: Introductionmentioning

confidence: 99%

“…One of these studies reported a trend in oxLDL reduction in untreated hypercholesterolemic subjects following 6 mmol of dietary nitrate supplementation [1]. Borsa et al [12] reported that systemic NO was negatively correlated with circulating oxLDL in hyperlipidemic elderly patients. Further studies are needed to better understand the use of dietary nitrate in relation to circulatory oxLDL in hypercholesterolemia and to further elucidate the dietary nitrate benefit on oxidative stress associated ED [1].…”

Section: Introductionmentioning

confidence: 99%

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The effect of dietary nitrate and vitamin C on endothelial function, oxidative stress and blood lipids in untreated hypercholesterolemic subjects: A randomized double-blind crossover study

et al. 2021

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Background: Vitamin C may enhance nitric oxide (NO) production through stepwise reduction of dietary nitrate (NO 3) to nitrite (NO 2) to NO. The combined effect of vitamin C and NO 3 supplementation is relatively unexplored in untreated hypercholesterolemia. Aims: We aimed to examine whether co-administration of vitamin C and nitrate for 4-weeks would improve endothelial function (primary outcome), plasma NO metabolites, oxidative stress, and blood lipids (secondary outcomes). Methods: Subjects 50e70 years of age with low density lipoprotein (LDL) > 130 mg/dL and RHI 2 were enrolled in this randomized double-blind crossover study. Subjects were assigned to two 4-week supplementation treatments starting with 70 ml of concentrated beetroot juice (CBJ) with 1000 mg of vitamin C (NC) or CBJ with matched placebo (N), then switched to alternate treatment following 2-week washout. The change in reactive hyperemia index (RHI), sum of plasma NO metabolites (NO 2 þ NO 3 (NOx)), oxidized LDL (oxLDL), and serum lipids were assessed at baseline and at 4-weeks of each treatment period. Results: Eighteen subjects (11M:7F) completed all study visits. No significant treatment differences were observed in RHI change (N: 0.21 ± 0.12; NC: 0.20 ± 0.17; p ¼ 0.99). Secondary analysis revealed that a subgroup of NC subjects who started with a baseline RHI of <1.67 (threshold value for ED) had greater improvements in RHI compared to subjects with RHI >1.67 (1.23 ± 0.15 to 1.96 ± 0.19; n ¼ 8 vs. 1.75 ± 0.11 to 1.43 ± 0.10; n ¼ 8; p ¼ 0.02). Compared to N, NC experienced a significant increase in plasma NOx (N: 94.2 ± 15.5 mmol/L; NC: 128.7 ± 29.1 mmol/L; p ¼ 0.01). Although there was no significant difference in oxLDL change between treatments (N: À1.08 ± 9.8 U/L; NC: À6.07 ± 9.14 U/L; p ¼ 0.19), NC elicited significant reductions in LDL (N: 2.2 ± 2; NC: À10.7 ± 23; p ¼ 0.049), triglycerides (N: 14.6 ± 43; NC: À43.7 ± 45; p ¼ 0.03), and no change in serum high density lipoprotein. Within treatment group comparisons showed that only NC reduced oxLDL significantly from baseline to 4 weeks (p ¼ 0.01). Conclusions: No between intervention differences were observed in RHI. RHI only improved in NC subjects with ED at intervention baseline. Four weeks of NC enriched the NO pool and promoted reduction of blood lipids and oxidative stress in subjects with hypercholesterolemia. These preliminary findings highlight a supplementation strategy that may reduce the progression of atherosclerotic disease and deserves further attention in studies using flow mediated dilation methods. Clinical trial registration: www.clinicaltrials.gov (NCT04283630).

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