RESUMO
AIMS: To investigate whether a specific endothelium-derived microparticles (EMPs) phenotype could be associated with birth weight and microvascular endothelial function in children. MATERIALS AND METHODS: A total of 95 children aged 6-14 years were recruited. Anthropometric measurements, blood pressure measurement, microvascular endothelial function testing, and biochemical profile analyses were performed. Standardized flow cytometry methods were used to identify and quantify the circulating CD144+, CD31+/annexin V+, and CD62E+ EMPs. KEY FINDINGS: The circulating number of CD31+/annexin V+ EMPs and CD144+ EMP levels were correlated with birth weight, systolic blood pressure, microvascular endothelial function, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) level. In the multivariable logistic regression models, we identified strong evidence of a higher risk of microvascular endothelial dysfunction among children with low birth weight (LBW) and increased levels of both CD31+/annexin V+ EMPs and LDL-C; LBW and elevated LDL-C levels were independent predictors of high circulating numbers of CD31+/annexin V+ and CD144+ > 75th percentile EMPs. SIGNIFICANCE: Our data provide evidence that children with LBW values showed greater numbers of circulating CD31+/annexin V+ and CD144+ EMPs. In addition, LBW and high levels of CD31+/annexin V+ and LDL-C were significant risk factors for the presence of microvascular endothelial dysfunction.
Assuntos
Micropartículas Derivadas de Células , Anexina A5 , Peso ao Nascer , LDL-Colesterol , Endotélio Vascular , HumanosRESUMO
BACKGROUND: Obesity perturbs endothelium integrity, leading to endothelial activation, which predisposes the release of endothelium-derived microparticles (EMP). We measured the CD31+/annexin V+ and CD62E+ EMP levels to improve our understanding of their contribution to endothelial damage in children with overweight/obesity. SUBJECT AND METHODS: In this cross-sectional study, 107 children with normal weight and 35 children with overweight/obesity were evaluated. Anthropometric measurement, blood pressure, biochemical profile was performed. Standardized flow cytometry methods were used to identify and quantify circulating CD31+/annexin V+ and CD62E+ EMP. RESULTS: Children with overweight/obesity had significantly higher circulating levels of CD31+/annexin V+ (750 [600]) and CD62E+ (1400 [700]) EMP than those with normal weight (P < 0.001 for both). We found that EMP levels were positively correlated with body mass index (BMI), waist circumference, blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDLc), and triglycerides. The multivariable logistic regression model revealed that the risks of having high EMP levels (> 75th percentile) were high in children with both large waist circumference and elevated LDLc level. Receiver operating characteristic (ROC) curves demonstrated that the LDLc levels showed significantly greater discrimination than waist circumference for both CD31+/annexin V+ (P = 0.031) as CD62E+ EMPs (P = 0.041). CONCLUSIONS: Children with overweight/obesity have high circulating CD31+/annexin V+ and CD62E+ EMP levels, which may be an early sign of endothelial apoptosis and inflammatory activation in response to injury. These EMP levels were positively associated with several cardiometabolic risk factors. Our data underscore the negative influence of high-risk metabolic profiles on endothelial integrity in the early stages of childhood obesity.
Assuntos
Sobrepeso , Obesidade Infantil , Anexina A5/metabolismo , Criança , LDL-Colesterol , Estudos Transversais , Endotélio Vascular , Humanos , Sobrepeso/complicações , Sobrepeso/metabolismo , Obesidade Infantil/complicaçõesRESUMO
BACKGROUND: There is increasing evidence that low birth weight has a negative effect on physical fitness, muscle strength, and cardiorespiratory endurance, although the findings are inconsistent. OBJECTIVES: This study aimed to evaluate whether birth weight acts as a prenatal determinant of physical fitness parameters and to determine the role of environmental or biological variables on this effect. METHODS: One hundred and sixty-seven children aged 6-14 years were included in this study. The anthropometric data, physical activity index, standing long jump, flexibility, handgrip strength, and cardiorespiratory fitness were evaluated. RESULTS: A positive correlation was found between birth weight and cardiorespiratory fitness (r = .349; p < .001), right handgrip strength (r = .337; p < .001), and left handgrip strength (r = .320; p < .001), suggesting that children with low birth weight had the worst performance in both cardiorespiratory endurance and grip strength tests. These findings remained significant after adjustment for prematurity, sex, age, physical activity index, and body mass index (BMI). Stepwise multiple regression analyses revealed a significant interaction of high birth weight, older age, and low BMI in predicting better cardiorespiratory endurance (R2 = .308). When handgrip strength was tested as the dependent variable, we found that high birth weight, male sex, and older age emerged as important determinants for both sides. CONCLUSION: Children aged 6-14 years born with a birth weight < 2.5 kg have low handgrip strength and cardiorespiratory fitness, which seems to be mediated partially by influences of both prenatal environment (e.g., birth weight) and biological variables (e.g., age, sex, BMI).
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Aptidão Cardiorrespiratória , Força da Mão , Idoso , Índice de Massa Corporal , Criança , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Força Muscular , Resistência Física , Aptidão Física , GravidezRESUMO
Irisin is an adipomyokine that increases browning of adipose tissue and thermogenesis, thereby protecting against obesity and insulin resistance. However, the correlation between irisin, brown adipose tissue (BAT), and childhood obesity, as well as its association with an increased risk of developing metabolic diseases, has not been completely elucidated. This study aimed to investigate the association between irisin levels and BAT activity measured by infrared thermography among children and verify their correlation with anthropometric and metabolic parameters. This study included 42 children with normal weight and 18 overweight/obese children. Anthropometric data, irisin levels, lipid and glucose profile were evaluated. The percentage of the thermally active portion of the supraclavicular area (%AreaSCR) before and after a cold stimulus was measured by infrared thermography, and the differences between the percentages of thermally active (Δ%AreaSCR) was calculated as an index of BAT activation. The results were correlated with anthropometric and metabolic parameters. Circulating irisin levels was positive correlated with age (rho=0.327, P= 0.011), body mass index (BMI) (rho=0.707, P<0.001), waist circumference (rho=0.624, P<0.001), total cholesterol (rho=0.361, P=0.044), triglycerides (rho=0.419, P=0.001), and low-density lipoprotein cholesterol (LDLc) (rho=0.381, P= 0.003). Active BAT was negatively correlated with BMI, waist circumference, triglycerides, LDLc and irisin levels. We observed that normal weight children increased significantly the Δ% AreaSCR as compared to overweight/obese children. In conclusion, circulating irisin levels and BAT activity appear to have opposing roles, since normal weight children had greater BAT activity and lower circulating levels of irisin.
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Tecido Adiposo Marrom/metabolismo , Fibronectinas/metabolismo , Obesidade Infantil/metabolismo , Criança , Feminino , Fibronectinas/sangue , Humanos , Masculino , Metaboloma , Obesidade Infantil/sangue , TermografiaRESUMO
PURPOSE: The involvement of the circulating endothelium-derived microparticles (EMPs) and the endothelial progenitor cells (EPCs) has been shown in the pathogenesis of coronary artery disease (CAD). The current study aimed to explore whether the Friesinger index is associated with the levels of the apoptotic CD144+/CD31+/annexin V+ âEMPs and the number of endothelial colony-forming units of progenitor cells in patients undergoing coronary angiography. PATIENTS AND METHODS: Fifty-seven patients with a median age of 62 years (range: 48-84 years) were enrolled. Quantification of the apoptotic CD144+/CD31+/annexin V+ EMPs was performed by flow cytometry. The number of endothelial colony-forming units defined by CFU-Hill was assessed by cell culture. RESULTS: There was a positive correlation between the Friesinger index and the circulating levels of the apoptotic CD144+/CD31+/annexin V+ EMPs (rho=0.817, p<0.001), whereas a negative correlation was found with the number of CFU-Hill (rho â= â- 0.649, p<0.001). Multivariable logistic analysis showed that the risk of having moderate/severe CAD was five times greater among male patients (OR:5.32; 95% CI: 1.19 - 16.33; p=0.038) and almost one and a half times higher among those with a higher level of apoptotic CD144+/CD31+/annexin V+ EMPs (OR:1.74; 95% CI: 1.23 - 2.28; p=0.001). Finally, the circulating levels of apoptotic EMPs labelled for CD144+/CD31+/annexin V+ presented a good discrimination of moderate/severe CAD, with an AUC of 0.85 (95% CI â= â0.74 - 0.96; p< 0.001). CONCLUSIONS: Moderate or severe CAD is associated with increased levels of apoptotic EMPs and reduced EPC colony-forming capacity, increasing the occurrence of endothelial injuries.
Assuntos
Micropartículas Derivadas de Células , Células Progenitoras Endoteliais , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Endotélio Vascular , Humanos , Masculino , Pessoa de Meia-Idade , Células-TroncoRESUMO
PURPOSE: The involvement of the circulating endothelium-derived microparticles (EMPs) and the endothelial progenitor cells (EPCs) has been shown in the pathogenesis of coronary artery disease (CAD). The current study aimed to explore whether the Friesinger index is associated with the levels of the apoptotic CD144þ/CD31þ/ annexin Vþ EMPs and the number of endothelial colony-forming units of progenitor cells in patients undergoing coronary angiography. Patients and METHODS: Fifty-seven patients with a median age of 62 years (range: 4884 years) were enrolled. Quantification of the apoptotic CD144þ/CD31þ/annexin Vþ EMPs was performed by flow cytometry. The number of endothelial colony-forming units defined by CFU-Hill was assessed by cell culture. RESULTS: There was a positive correlation between the Friesinger index and the circulating levels of the apoptotic CD144þ/CD31þ/annexin Vþ EMPs (rho»0.817, p< 0.001). CONCLUSIONS: Moderate or severe CAD is associated with increased levels of apoptotic EMPs and reduced EPC colony-forming capacity, increasing the occurrence of endothelial injuries.
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Doença da Artéria Coronariana , Angiografia Coronária , Endotélio/patologiaRESUMO
Previous reports reveal that +9/-9 polymorphism of the bradykinin B2 receptor (BDKRB2) is suggestive of cardiometabolic diseases. The aim of this study was to examine the impact of BDKRB2 + 9/-9 polymorphism genotypes on the blood pressure parameters and microvascular function in prepubescent children. We screened for BDKRB2 + 9/-9 polymorphism in the DNA of 145 children (86 boys and 59 girls), and its association with body composition, blood pressure levels, biochemical parameters, and endothelial function was determined. No significant association of the BDKRB2 genotypes with gender (P=0.377), race (P=0.949) or family history of cardiovascular disease (CVD) (P=0.858) was observed. Moreover, we did not identify any interaction between BDKRB2 genotypes with a phenotype of obesity (P=0.144). Children carrying the +9/+9 genotype exhibited a significant linear trend with higher levels of systolic blood pressure and pulse pressure (P<0.001). Moreover, the presence of +9 allele resulted in a decrease of reactive hyperemia index, showing a decreasing linear trend from -9/-9 to +9/+9, wherein this parameter of endothelial function was the lowest in the +9/+9 children, intermediate in the +9/-9 children, and the highest in the -9/-9 children (P<0.001). There was a significant inverse correlation between reactive hyperemia index and systolic blood pressure (r= - 0.348, P< 0.001) and pulse pressure (r= - 0.399, P< 0.001). Our findings indicate that the +9/+9 BDKRB2 genotype was associated with high blood pressure and microvascular dysfunction in prepubescent Brazilian children.
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Pressão Sanguínea/genética , Síndrome Metabólica/genética , Microcirculação/genética , Polimorfismo Genético , Receptor B2 da Bradicinina/genética , População Negra/genética , Brasil/epidemiologia , Criança , Feminino , Genótipo , Humanos , Hiperemia/genética , Hiperemia/fisiopatologia , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Grupos Raciais/genética , População Branca/genéticaRESUMO
Hypertension (HTN) remains a common complication after kidney transplantation among paediatric patients. Although low birth weight (LBW) has been implicated as an important risk factor for cardiovascular diseases, its effect on transplantation patients has not yet been addressed. It is essential to determine whether children with LBW who undergo transplantation are more likely to develop post-transplantation HTN. For this study, the medical records of 96 kidney recipients were retrospectively examined. A total of 83 patients fulfilled the inclusion criteria. Overall, post-transplantation HTN was observed in 54% of the recipients. Multivariate logistic regression revealed that time from transplantation >14 months (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.31-10.06; P = 0.013), current CKD (OR 2.6; 95% CI 1.01-7.20; P = 0.045), presence of LBW (OR 3.6; 95% CI 1.04-12.32; P = 0.044) and current overweight/obesity (OR 3.7; 95% CI 1.02-13.91; P = 0.047) were associated with post-transplantation HTN. In conclusion, our data provide evidence for the first time that LBW is a significant predictive factor in the development of post-transplantation HTN. This finding has important clinical implications as it serves to alert clinicians about this additional risk factor in paediatric patients undergoing kidney transplant.
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Peso ao Nascer , Hipertensão/epidemiologia , Transplante de Rim/efeitos adversos , Insuficiência Renal Crônica/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Hipertensão/etiologia , Incidência , Masculino , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Fatores de RiscoRESUMO
OBJECTIVE: To provide a comprehensive assessment of the relationship of birth weight with both endothelial progenitor cell function and angiogenic factors in children. STUDY DESIGN: Anthropometric measures, biochemical profile, endothelial progenitor cell number, endothelial progenitor cell colony-forming units, vascular endothelial growth factor-A, and nitric oxide plasma levels of 58 children aged 7-11 years were determined. RESULTS: A positive correlation was observed between birth weight and circulating endothelial progenitor cell number (r= 0.461; P= .001), endothelial progenitor cell colony-forming units (r= 0.512; P < .001), vascular endothelial growth factor-A (r= 0.407; P= .002), and nitric oxide (r= 0.547; P < .001) levels, whereas the adjustment for prematurity, family history of cardiovascular disease, and systolic blood pressure levels did not modify these associations. CONCLUSION: Low birth weight was associated with a decrease in the circulating/functional capacity of endothelial progenitor cells among healthy children, independent of traditional cardiovascular risk factors. This detrimental impact was accompanied by lower circulating levels of angiogenic factors.
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Antropometria , Células Progenitoras Endoteliais/citologia , Recém-Nascido de Baixo Peso , Neovascularização Fisiológica , Óxido Nítrico/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Peso ao Nascer , Pressão Sanguínea , Peso Corporal , Doenças Cardiovasculares/sangue , Criança , Feminino , Voluntários Saudáveis , Humanos , Recém-Nascido , Leucócitos Mononucleares/citologia , Masculino , Fatores de Risco , Células-Tronco/citologia , Inquéritos e Questionários , SístoleRESUMO
Genetic, social, and environmental conditions contribute to the development of depression, but the pathophysiological mechanisms are still unclear. Data accumulated in recent years provide significant evidence for a direct role of galanin (GAL). This study aimed to investigate the relation between SNPs in the galaninergic system and depressive symptoms in adolescents. A total of112 adolescents aged 10-18years participated in this study. The Children Depression Inventory (CDI) was used to evaluate depressive symptoms. The effects of rs948854 and rs4432027 SNPs, both located within the promoter region of the GAL gene, rs11665337 in the GALR1 receptor, and rs8836 in the GALR2 receptor on depressive symptoms were examined. The results indicated that 30.4% of the participants had depression. We found that girls were significantly more likely to be depressive than boys. Furthermore, rs948854 minor (G) allele was associated with depressive symptoms. Adolescents carrying the GG and AG genotype for the A/G (rs948854) SNP showed higher CDI scores than those carrying homozygous AA. The binomial logistic regression analysis revealed that adolescents carrying the GG genotype at SNP rs948854 had a higher likelihood of being depressive than adolescents carrying the AA or AG genotypes (P=0.033). Moreover, individuals whose mothers had a positive history for depression and who were sedentary were more likely to display depressive symptoms (P=0.013 and P=0.032, respectively). In conclusion, the SNP rs948854 in the GAL gene seems to be involved in the modulation of depressive state, especially in individuals with GG genotype.