Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children

Khalyfa, Abdelnaby; Kheirandish‐Gozal, Leila; Bhattacharjee, Rakesh; Khalyfa, Ahamed; Gozal, David

doi:10.1378/chest.15-0799

Cited by 71 publications

(61 citation statements)

References 69 publications

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“…A large number of miRNAs were identified as intrinsic in the pathogenesis of insulin resistance by affecting pancreatic β-cell development, insulin biosynthesis, insulin secretion, or by interacting with insulin signaling pathways [81]. In addition, several miRNAs proved to be associated with endothelial dysfunction [83], serum lipid level alterations [78, 84, 85], inflammation [86], and other additional markers of metabolic dysfunction in children [85]. Interestingly, some miRNAs are enriched in the hypothalamus, suggesting a primary role in the hypothalamic regulation of energy intake, expenditure, and body weight control [87].…”

Section: The Role Of Epigenetics and Developmental Programming In Thementioning

confidence: 99%

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

Bussler¹,

Penke²,

Flemming³

et al. 2017

Horm Res Paediatr

103

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Metabolic syndrome (MetS) is recognized as an escalating major health risk in adults as well as in children and adolescents. Its prevalence ranges from 6 to 39% depending on the applied definition criteria. To date, there is no consensus on a MetS definition for children and adolescents. However, most authors agree on essential components such as glucose intolerance, central obesity, hypertension, and dyslipidemia; each representing a risk for cardiovascular disease. Recently, associations between MetS and non-alcoholic fatty liver disease, hyperuricemia, and sleep disturbances have emerged. Biomarkers like adipocytokines are a subject of current research as they are implicated in the pathogenesis of the MetS. Epigenetics and gestational programming, especially the role of microRNA, comprise a novel, rapidly developing and promising research focus on the topic of MetS. MicroRNAs are increasingly valued for potential roles in the diagnosis, stratification, and therapeutics of MetS. Early detection of risk factors, screening for metabolic disturbances, and the identification of new therapies are major aims to reduce morbidity and mortality related to MetS. Dietary modification and physical activity are currently the only adopted treatment approaches. Pharmacological therapies and bariatric surgery are still contradictory and, therefore, are only recommended in selected high-risk cases.

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Section: The Role Of Epigenetics and Developmental Programming In Thementioning

confidence: 99%

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

Bussler¹,

Penke²,

Flemming³

et al. 2017

Horm Res Paediatr

103

View full text Add to dashboard Cite

show abstract

“…MicroRNAs are small non‐coding RNAs (~22 nucleotides) that function in the post‐transcriptional regulation of gene expression. Several recent studies have evaluated their potential as biomarkers in a variety of paediatric conditions, including diabetes, endothelial dysfunction in obesity, leukaemia, asthma, autism and cholestatic liver disease . In addition to the possibility of improved sensitivity and specificity, miRNAs may appear in the serum earlier in disease progression than many commonly assayed protein biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Elevation of circulating microRNA levels in obese children compared to healthy controls

et al. 2017

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As childhood obesity increases, it is becoming important to understand the complications of obesity in children and develop novel biomarkers. Evidence indicates that microRNAs (miRNA) are dys-regulated in obesity and may serve as sensitive and specific circulating biomarkers. Non-alcoholic fatty liver disease (NAFLD) is a complication of obesity that ultimately requires a liver biopsy to determine disease severity. While studies have been conducted in adults, no study to date has examined circulating miRNAs in children with obesity and NAFLD. The goal of this study was to evaluate a panel of selected circulating miRNAs in obese children compared to healthy controls. We present here an analysis of a pre-selected panel of 20 candidate miRNAs in obese children compared to healthy controls. The miRNAs were chosen based on having been previously reported to be involved in NAFLD. We found that 16 out of 20 miRNAs tested were elevated at least twofold in children with obesity compared to controls. miR-122 and miR-199a showed the greatest increase in children with obesity versus controls. Both also had a high area under the curve when receiver-operator curves were plotted. Several circulating miRNAs correlated with body mass index (BMI) or serum transaminases. This study provides initial evidence that circulating miRNAs can be measured in the paediatric population and provides several diagnostic candidates increased in children with obesity that may be relevant to NAFLD.

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“…The time to maximal regional blood flow after occlusion release (T max ) is representative of the postocclusion hyperemic response, an index of NO-dependent endothelial function. 27 A T max >45 seconds was considered as indicative of abnormal endothelial function 28,29 and represents 3 standard deviations above the mean. The intraobserver and interobserver variability of the test have been previously examined and are 8.9% and 13.8%, respectively.…”

Section: Endothelial Function Measurementsmentioning

confidence: 99%

“…The intraobserver and interobserver variability of the test have been previously examined and are 8.9% and 13.8%, respectively. 29 According to our recruitment strategies, 4 distinctly different groups of children were identified: Controls (CO), who were nonobese and either nonsnoring or snoring children with normal polysomnographic tests; obese children (OB), ie, BMI z-score ≥1.65 with either normal polysomnographic tests or evidence of OSA; and nonobese snoring children with abnormal polysomnographic findings confirming the presence of OSA.…”

Section: Endothelial Function Measurementsmentioning

confidence: 99%

Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

Kheirandish‐Gozal

Philby

Qiao

et al. 2017

JAHA

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Background--Obstructive sleep apnea (OSA) is a highly prevalent condition, especially in obese children, and has been associated with increased risk for endothelial dysfunction and dislipidemia, which are precursors of atherosclerosis. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is recognized as an independent risk factor for cardiovascular risk and atheromatous plaque activity. We hypothesized that Lp-PLA2 levels would be elevated in children with OSA, particularly among obese children who also manifest evidence of endothelial dysfunction.

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Circulating microRNAs as Potential Biomarkers of Endothelial Dysfunction in Obese Children

Cited by 71 publications

References 69 publications

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

Novel Insights in the Metabolic Syndrome in Childhood and Adolescence

Elevation of circulating microRNA levels in obese children compared to healthy controls

Endothelial Dysfunction in Children With Obstructive Sleep Apnea Is Associated With Elevated Lipoprotein‐Associated Phospholipase A2 Plasma Activity Levels

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