Dano endotelial e associações cardiometabólicas na obesidade infantil: quantificação de micropartículas CD62E+ E CD31/Anexina V+ derivadas do endotélio em crianças com sobrepeso e obesidade
Data
2021-11-25
Orientadores
Franco, Maria do Carmo Pinho 
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: O aumento da incidência de obesidade durante a infância é preocupante e pode preceder o desenvolvimento de aterosclerose. Essa condição metabólica prejudica a integridade do endotélio, levando a ativação endotelial, o que predispõem a liberação de micropartículas derivadas do endotélio (MPEs). Analisamos os níveis de MPEs CD31+/anexina V+ e CD62E+, para melhorar nosso entendimento de suas contribuições para o dano endotelial em crianças com sobrepeso/obesidade. Objetivos/Métodos: 107 crianças com peso normal e 35 crianças com sobrepeso/obesidade foram avaliadas. Dados antropométricos, níveis pressóricos e perfil bioquímico também foram avaliados. Métodos padronizados de citometria de fluxo foram usados para identificar e quantificar as micropartículas endoteliais circulantes CD31+/Anexina V+ e CD62E+. Resultados: Crianças com sobrepeso/obesidade apresentaram níveis significantemente elevados de ambas as MPEs comparadas com aqueles com peso normal (P 75°) foram maiores nas crianças com circunferências de cintura grandes e níveis de LDLc elevados. A relação de MPE CD62E+/CD31+ foi mais alta nas crianças com sobrepeso/obesidade do que naquelas com peso normal, refletindo um desequilíbrio entre as células endoteliais ativadas e apoptóticas. Por fim, foram construídas as curvas ROC comparando a capacidade discriminante da circunferência de cintura e níveis de LDLc. Descobrimos que os níveis de LDLc mostraram discriminação significantemente maior do que a circunferência de cintura para ambas as MPEs, tanto para CD31+/Anexina V+ (P= 0.031) quando para CD62E+ (P= 0.041). Conclusão: Crianças com sobrepeso/obesidade tem maiores níveis circulantes de CD31+/Anexina V+ e CD62E+, o que pode ser um indício precoce de apoptoses e ativação inflamatória endotelial em resposta a lesão. Esses níveis de MPE são positivamente associados com vários fatores de riscos cardiometabólicos. Nossos dados ressaltam a influência negativa dos altos perfis de riscos metabólicos na integridade endotelial em estágios iniciais da obesidade infantil.
Background: The increasing incidence of obesity during childhood is disturbing and can precede atherosclerosis development. This metabolic condition perturbs endothelium integrity, leading to endothelial activation, which predisposes the release of endotheliumderived microparticles (EMPs). 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. Subjects/Methods: 107 children with normal weight and 35 children with overweight/obesity were evaluated. Anthropometric data, blood pressure levels, biochemical profile were also evaluated. Standardized flow cytometry methods were used to identify and quantify circulating CD31+/annexin V+ and CD62E+ EMPs. Results: Children with overweight/obesity had significantly higher circulating levels of both EMPs than those with normal weight (P<0.001). 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. The CD62E+/CD31+ EMP ratio was higher in children with overweight/obesity than that in those with normal weight, reflecting an imbalance between endothelial cell activation and apoptosis. Finally, ROC curves comparing the discriminating ability of waist circumference and LDLc levels were constructed. We found 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.
Background: The increasing incidence of obesity during childhood is disturbing and can precede atherosclerosis development. This metabolic condition perturbs endothelium integrity, leading to endothelial activation, which predisposes the release of endotheliumderived microparticles (EMPs). 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. Subjects/Methods: 107 children with normal weight and 35 children with overweight/obesity were evaluated. Anthropometric data, blood pressure levels, biochemical profile were also evaluated. Standardized flow cytometry methods were used to identify and quantify circulating CD31+/annexin V+ and CD62E+ EMPs. Results: Children with overweight/obesity had significantly higher circulating levels of both EMPs than those with normal weight (P<0.001). 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. The CD62E+/CD31+ EMP ratio was higher in children with overweight/obesity than that in those with normal weight, reflecting an imbalance between endothelial cell activation and apoptosis. Finally, ROC curves comparing the discriminating ability of waist circumference and LDLc levels were constructed. We found 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.
Descrição
Citação
THOMAZINI, F. Dano endotelial e associações cardiometabólicas na obesidade infantil: quantificação de micropartículas CD62E+ E CD31/Anexina V+ derivadas do endotélio em crianças com sobrepeso e obesidade. 61 f. Dissertação (Mestrado em Medicina Translacional) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2021.