Myeloperoxidase overexpression in children with hypercholesterolemia

Pignatelli, Pasquale; Loffredo, Lorenzo; Martino, Francesco De; Catasca, Elisa; Carnevale, Roberto; Zanoni, Cristina; Ben, Maria Del; Antonini, R; Basili, Stefania

doi:10.1016/j.atherosclerosis.2008.10.025

Cited by 18 publications

(17 citation statements)

References 22 publications

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“…An implication of this finding is that the increase in ox-LDL in obese patients should be attributed to other ROS-generating enzymes, which is in agreement with our previously published observations of a significant association between serum ox-LDL and myeloperoxidase, which suggested a role for this enzyme in generating ox-LDL in vivo. 27 Hence, in patients at risk of cardiovascular disease such as those with obesity, the coexistence of high values of different markers of oxidative stress suggests that Ͼ1 ROS-generating pathway is upregulated.…”

Section: Violi Et Almentioning

confidence: 99%

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation

et al. 2009

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Background-NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). Methods and Results-Twenty-five patients with hereditary deficiency of gp91 phox , the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91 phox , serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91 phox expression was downregulated in X-CGD patients (1.0Ϯ0.8 mean fluorescence; PϽ0.001) and upregulated in obese patients (4.1Ϯ2.2 mean fluorescence; Pϭ0.01) compared with healthy subjects (2.9Ϯ1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7Ϯ33.3 pg/mg creatinine; Pϭ0.04) and increased in obese patients (154.4Ϯ91 pg/mg creatinine; PϽ0.001) compared with healthy subjects (69.5Ϯ52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3Ϯ6.7 versus 24.8Ϯ9.8 U/L; PϽ0.001) and X-CGD patients (28.5Ϯ7.2 U/L; PϽ0.001). X-CGD patients had significantly higher FMD (14.7Ϯ5.9%) compared with healthy subjects (7.9Ϯ2.5%; PϽ0.001); obese patients had lower FMD (5.3Ϯ3.0%; Pϭ0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0Ϯ10.8 mol/L; Pϭ0.016) and lower in obese patients (9.3Ϯ11.0 mol/L; Pϭ0.001) compared with healthy subjects (27.1Ϯ19.1 mol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R s ϭ0.403, PϽ0.001) and platelet gp91 phox (R s ϭϪ0.515, PϽ0.001). FMD inversely correlated with platelet gp91 phox (R s ϭϪ0.502, PϽ0.001) and isoprostanes (R s ϭϪ0.513, PϽ0.001). Conclusion-This study provides the first evidence that, in humans, gp91 phox is implicated in the modulation of arterial tone.

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Section: Violi Et Almentioning

confidence: 99%

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation

et al. 2009

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“…Data on the predictive value of MPO in early atherosclerosis in children are very limited. Pignatelli et al (25) reported that MPO increased and significantly correlated with ox-LDL and 8-OHdG levels in children with hypercholesterolemia, but their study does not give any data on whether MPO is the cause or the consequence of dyslipidemia, due to the lack of evidence of atherosclerosis such as cIMT and FMD. We found an elevation in MPO activities in patients undergoing treatment with lipid apheresis, and all these patients have had cholesterol levels higher than 300 mg/dL.…”

Section: Discussionmentioning

confidence: 93%

“…The groups were evaluated with regard to their age; 11 of the patients and 9 of the controls were under the age 25 of 6 years. While myocardial performance (p = 0.037) was lower in patients than in age-matched controls, cholesterol (p = 0.001), LDL-cholesterol (p = 0.001), triglyceride (p = 0.05), ChT (p = 0.02), basal TBARS (p = 0.01), stimulated TBARS (p = 0.001) and IL-6 (p = 0.045) levels were higher.…”

Section: Resultsmentioning

confidence: 99%

“…MPO generates a number of reactive species that promote further oxidative modifications of LDL and may also lead to cross-linking and aggregation (24). Recently, many investigations focused on the role of MPO in atherosclerosis (24)(25)(26) because of its dual role (inflammation and oxidative stress). Schindhelm et al (24) reported that enhanced levels of MPO were correlated with higher risk for myocardial infarction and/or mortality rate in coronary heart disease patients aged 40 and older.…”

Section: Discussionmentioning

confidence: 99%

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Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children

Kologlu

Uçar

Levent

et al. 2014

Journal of Pediatric Endocrinology and Metabolism

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A correlation has been clearly shown between inflammation markers and subclinical atherosclerosis markers in the early stages of atherogenesis in subjects with familial hypercholesterolemia (FH). The aim of this study was to investigate potential inflammation markers in the diagnosis of atherosclerosis in children with FH. A total of 48 dyslipidemic children and 24 healthy age-matched control subjects were taken into study. Inflammation and macrophage activation markers (hsCRP, myeloperoxidase, chitotriosidase, YKL-40, TNF-α, IL-6, IL-18, MMP-1 and MMP-9) and lipid parameters of all patients were measured. Carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD) levels were determined. Our data suggested that clinically evidenced (by cIMT and FMD levels) atherosclerosis starts in the early ages in hypercholesterolemic children. Higher cholesterol levels strongly correlated with macrophage activation markers (ChT, YKL-40 and myeloperoxidase). ChT and YKL-40 seem to be the more predictable markers of atherosclerosis even in early ages (<6 years old) than other classical inflammation markers such as hs-CRP, IL-6 and TNF-α.

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“…Hypercholesterolemia is associated with enhanced levels of oxidative stress from infancy [68]. To modulate cholesterol-related oxidative stress, Cadoner-Franc et al performed an interventional trial by giving mandarin juice to hypercholesterolemic children.…”

Section: Nutraceuticals and Hypercholesterolemiamentioning

confidence: 99%

Nutraceuticals in the Early Infancy

Pignatelli¹,

Basili²

2010

Cardiovascular Therapeutics

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Atherosclerosis disease and its extent in childhood correlate positively with established risk factors, namely obesity, hypercholesterolemia, diabetes mellitus, and hypertension. The safety and efficacy of some dietary interventions to modulate risk factors in childhood are documented by an increasing body of evidence. The present review analyzes nutritional and nutraceutical current strategies addressed to modify some risk factors of atherosclerosis in childhood. In particular, studies concerning nutrients such as fibers, omega-3-fatty acids, vitamin D, antioxidants, and calcium have been evaluated. An overall analysis suggests that some nutraceuticals might represent an attractive tool to lower the development of atherosclerotic-related cardiovascular complication in children. Nevertheless, at this moment, due to the methodological weakness that characterizes the majority of the analyzed studies, nutrients or supplements should not be considered as a therapeutic tool potentially usable for clinical purpose in children at risk for cardiovascular disease.

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Myeloperoxidase overexpression in children with hypercholesterolemia

Cited by 18 publications

References 22 publications

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation

Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children

Nutraceuticals in the Early Infancy

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Myeloperoxidase overexpression in children with hypercholesterolemia

Cited by 18 publications

References 22 publications

Hereditary Deficiency of gp91 phox Is Associated With Enhanced Arterial Dilatation

Hereditary Deficiency of gp91 phox Is Associated With Enhanced Arterial Dilatation

Chitotriosidase as a possible marker of clinically evidenced atherosclerosis in dyslipidemic children

Nutraceuticals in the Early Infancy

Contact Info

Product

Resources

About

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation

Hereditary Deficiency of gp91 ^phox Is Associated With Enhanced Arterial Dilatation