RESUMO
MicroRNAs (miRNAs/miRs) are involved in the pathogenesis of diabetes mellitus and its chronic complications, and their circulating levels have emerged as potential biomarkers for the development and progression of diabetes. However, few studies have examined the expression of miRNAs in diabetic retinopathy (DR) in humans. This case-control study aimed to investigate whether the plasma levels of miR-29b and miR-200b are associated with DR in 186 South Brazilians with type 2 diabetes (91 without DR, 46 with non-proliferative DR and 49 with proliferative DR). We also included 20 healthy blood donors to determine the miRNA expression in the general population. Plasma levels of miR-29b and miR-200b were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Proliferative DR was inversely associated with plasma levels of miR-29b (unadjusted OR = 0.694, 95% CI: 0.535-0.900, P = 0.006) and miR-200b (unadjusted OR = 0.797, 95% CI: 0.637-0.997, P = 0.047). However, these associations were lost after controlling for demographic and clinical covariates. In addition, patients with type 2 diabetes had lower miR-200b levels than blood donors. Our findings reinforce the importance of addressing the role of circulating miRNAs, including miR-29 and miR-200b, in DR.
Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , MicroRNAs/genética , Estudos de Casos e Controles , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Feminino , Seguimentos , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos ProspectivosRESUMO
CONTEXT: Matrix metalloproteinases are involved in atherosclerosis and plaque vulnerability. OBJECTIVE: To investigate serum levels and genetic polymorphisms of matrix metalloproteinases (MMPs) -1, -3 and -9 in patients submitted to carotid endarterectomy. METHODS: Genetic polymorphisms were evaluated using polymerase chain reaction (PCR-RFLP); serum levels were measured using ELISA; histological sections were stained with Picrosirius Red to analyze the fibrous cap thickness, lipid core and collagen content and with hematoxylin--eosin to detect the presence of intraplaque hemorrhage. RESULTS: MMP-9 serum levels were significantly higher in patients with a thinner fibrous cap (p = 0.033) or acute or recent intraplaque hemorrhage (p = 0.008) on histology, as well as in patients with previous stroke (p = 0.009) or peripheral vascular disease (p = 0.049). No consistent associations were observed between different MMP genotypes and fibrous cap thickness, lipid core, collagen content or intraplaque hemorrhage. CONCLUSIONS: MMP-9 serum levels were consistently associated with markers of carotid atherosclerosis and lesion vulnerability, whereas specific MMP genotypes were not.
Assuntos
Doenças das Artérias Carótidas/enzimologia , Metaloproteinase 9 da Matriz/sangue , Idoso , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/genética , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RadiografiaRESUMO
MicroRNAs are associated with myocardial damage and heart failure (HF). The present study investigated whether the plasma levels of microRNA (miR)21, 126 and 4235p alter according to the (de)compensated state of patients with HF and are associated with allcause mortality. In 48 patients with HF admitted to the emergency room for an episode of acute decompensation, blood samples were collected to measure miR and Btype natriuretic peptide levels within 24 h of hospital admission, at the time of hospital discharge, and a number of weeks postdischarge (chronic stable compensated state). Levels of miR21, miR126 and miR4235p increased between admission and discharge, and decreased following clinical compensation. During followup (up to 48 months), 38 patients (79%) were rehospitalized at least once and 21 patients (44%) succumbed. Patients who had increased levels of miR21 and miR126 at the time of clinical compensation exhibited better 24month survival and remained rehospitalizationfree for a longer period compared with those with low levels. Additionally, patients whose levels of miR4235p increased between admission and clinical compensation experienced fewer hospital readmissions in the 24 months following the time of clinical compensation compared with those who had decreased levels. It was concluded that the plasma levels of miR21, miR126 and miR4235p altered during clinical improvement and were associated with the prognosis of acute decompensated HF.