Cardiovascular Consequences of Childhood Obesity

McCrindle, Brian W.

doi:10.1016/j.cjca.2014.08.017

Cited by 127 publications

(89 citation statements)

References 70 publications

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“…Obesity is a frequent condition in children that carries a substantial risk for cardiovascular disease (CVD) later in life (1)(2)(3). Similarly, obstructive sleep apnea (OSA) is a highly prevalent pediatric disorder typically associated with a higher risk for future cardiovascular morbidity, primarily presenting as increased systemic blood pressure deregulation that can lead to ventricular remodeling, and altered endothelial function, an early precursor of atherosclerosis, the latter being improved by treatment of OSA with adenotonsillectomy (Tx) (4)(5)(6)(7).…”

mentioning

confidence: 99%

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Khalyfa¹,

Kheirandish‐Gozal²,

Khalyfa³

et al. 2016

Am J Respir Crit Care Med

106

110

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Rationale: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells.Objectives: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status.Methods: Obese children (body mass index z score .1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cellsubstrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays.Measurements and Main Results: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways.Conclusions: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.

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mentioning

confidence: 99%

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Khalyfa¹,

Kheirandish‐Gozal²,

Khalyfa³

et al. 2016

Am J Respir Crit Care Med

106

110

View full text Add to dashboard Cite

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“…Due to the anatomic and functional derangement of adipose tissue with increased body fat, adverse health consequences include both 'sick fat disease' (adiposopathy, as shown in Table 1) and 'fat mass disease' 1 , with this latter term intended to describe the adverse health consequences predominantly due to an increase in fat mass (e.g., stress on weight bearing joints, immobility, tissue compression, and tissue friction) 10 . Adverse adiposopathic consequences can occur early in life, as evidenced by the contribution of adipocyte and adipose tissue endocrinopathies, immunopathies, and oxidative stress, which manifest in cardiometabolic disturbances in children (and adults) with obesity 11,12 .…”

Section: Pathogenic Potential Of Adipose Tissuementioning

confidence: 99%

Adiposopathy and epigenetics: an introduction to obesity as a transgenerational disease

Bays

Scinta²

2015

Current Medical Research and Opinion

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“…Childhood obesity is recognized as a global health care problem especially in developed countries [1,2]. The American Heart Association stresses the importance of obesity as an independent but modifiable risk factor for coronary artery disease, ventricular dysfunction, congestive heart failure and cardiac arrhythmias [3,4].…”

Section: Introductionmentioning

confidence: 99%

Çocukluk çağı obezitesinin kardiyak yapı ve fonksiyonlara etkisi

Atik¹,

Şanlı²,

Ergür³

et al. 2017

TURKISH JOURNAL of CLINICS and LABORATORY

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The aim of this study was to compare the left ventricle structure and its functions in obese children without established complications and none obese children. Material and Methods:Anthropometric and conventional echocardiographic parameters of cardiac geometry and left ventricular function were obtained in 40 obese children without any other disease and complication of obesity like hypertension, hypercholesterolemia, and a control group of 40 healthy lean. Fasting plasma glucose, insulin levels were obtained and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated.Results: Height, weight, body surface area and body mass index (BMI), were found significantly higher in the obese group (P < 0.001). Insulin and HOMA-IR scores were higher in obese group. No significant differences were observed for left ventricular systolic and diastolic diameter (P > 0.05). Left ventricular mass (LVM), LVM/ht, LVM/BMI and relative wall thickness (RWT) were significantly increased in obese children than the controls (P < 0.001) and most of them had eccentric left ventricular (LV) hypertrophy. Ejection fraction was significantly decreased seen obese group. A positive correlation was seen between BMI and LV posterior wall thickness and interventricular septal thickness (R > 0.45, P < 0.05). Both types of hypertrophy were seen in insulin resistant obese group. Conclusion:The known causes are altered homeostatic and neurohumoral mechanisms and compensation of higher metabolic demands and increased left ventricular mass, reduced myocardial performance due to hemodynamic load associated with higher cardiovascular morbidity and mortality rates.

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Cardiovascular Consequences of Childhood Obesity

Cited by 127 publications

References 70 publications

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

Adiposopathy and epigenetics: an introduction to obesity as a transgenerational disease

Çocukluk çağı obezitesinin kardiyak yapı ve fonksiyonlara etkisi

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