RESUMO
This study aims to investigate the association of peroxisome proliferator-activated receptor (PPAR) delta -87T/C polymorphism with several sugar metabolism indices and tumor necrosis factor α (TNF α) level. The body mass index (BMI), waist size, and levels of fasting plasma glucose, serum lipid, fasting insulin, TNFα, and PPAR delta -87T/C of 286 patients with type 2 diabetes mellitus (T2DM) and 158 subjects with normal fasting glucose (NFG) were measured in a Dalian population. The distribution of genotypic frequencies between T2DM and NFG were not significantly different (χ(2) = 0.012, P = 0.994). BMI, fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), triglyceride, and TNFα levels were significantly different among different T2DM genotypes. HOMA-IR and FBG were significantly different among different NFG genotypes. The PPAR delta -87T/C polymorphism is known to be closely related with glucose levels and lipid metabolism. A close relationship was also found between HOMA-IR and TNFα levels and HOMA-IR and FBG in T2DM and NFG, respectively.
Assuntos
Diabetes Mellitus Tipo 2/genética , Obesidade/genética , PPAR delta/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/genética , Idoso , Alelos , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Jejum , Feminino , Frequência do Gene , Genótipo , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , PPAR delta/metabolismo , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Assuntos
Animais , Masculino , Cardiomegalia/genética , Regulação para Baixo/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/genética , Regulação para Cima/genética , Algoritmos , Aorta/cirurgia , Biomarcadores , Biologia Computacional , Constrição Patológica/genética , Modelos Animais de Doenças , Prognóstico , Ratos Sprague-DawleyRESUMO
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.