RESUMO
An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-interacting protein (TXNIP), which was then knocked-down to investigate its effects on myocardial remodeling, followed by detection on myocardial infarction size (MIS), myocardial collagen volume fraction (CVF) and cardiomyocyte apoptosis. MSCs-derived EVs carrying miR-150-5p were cultured with neonatal cardiomyocytes under hypoxia/hypoglycemia condition for in vitro exploration and intramyocardially injected into I/R rats for in vivo exploration. I/R-induced rats presented higher TXNIP levels and lower miR-150-5p levels, along with increased cardiomyocyte apoptosis. miR-150-5p in MSCs was transferred through EVs to cardiomyocytes, leading to suppressed myocardial remodeling, as reflected by smaller MIS and CVF and suppressed cardiomyocyte apoptosis. I/R-treated rats injected with MSCs-derived EVs containing miR-150-5p showed a reduction in myocardial remodeling associated with the downregulation of TXNIP, which may be clinically applicable for treatment of I/R.
Assuntos
Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs , Traumatismo por Reperfusão/metabolismo , Animais , Apoptose/efeitos dos fármacos , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Recently, it has been reported that the A930G and C242T polymorphisms within p22phox (CYBA) gene are involved in the pathogenesis of hypertension. However, the results remain controversial. Furthermore, no previous meta-analysis has been conducted to evaluate the relationship between the A930G and C242T polymorphisms and hypertension. Therefore, we performed this meta-analysis to clarify these controversies. OBJECTIVE AND METHODS: All of the included articles were retrieved from the PubMed and Embase databases, as well as the CNKI, CBM, Chongqing VIP and Wan Fang databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were used to assess the strength of the association. Accounting for heterogeneity, a fixed or random effects model was respectively adopted. Heterogeneity was checked using the Q test and the I(2) statistic. A cumulative meta-analysis was conducted to estimate the tendency of pooled OR. Funnel plots and Egger's tests were performed to test for possible publication bias. RESULTS: Five articles on A930G with 2003 cases/2434 controls and eight articles on C242T with 2644 cases/1967 controls were identiï¬ed. A signiï¬cant association of A930G polymorphisms with the risk of hypertension was found in the dominant model (OR=0.59, 95% CI: 0.38-0.92, p=0.021) and allelic model (OR=0.66, 95% CI: 0.46-0.95, p=0.024). In the stratified analysis, a signiï¬cant association could be found among the hospital-based and population-based studies. However, no evidence of a significant association of the C242T polymorphism with hypertension was found in the overall analysis and subgroup analysis. CONCLUSIONS: This meta-analysis indicates that the A930G polymorphism, but not the C242T variation, might be a protective factor for hypertension.
Assuntos
Substituição de Aminoácidos , Hipertensão/genética , NADPH Oxidases/genética , Polimorfismo de Nucleotídeo Único , Alelos , Predisposição Genética para Doença , Humanos , Razão de Chances , Viés de PublicaçãoRESUMO
Ischemic stroke (IS) is a complex multifactorial inherited disease. Many studies have focused on the potential genetic effects of apolipoprotein E (ApoE) gene polymorphism on IS. However, inconsistencies still exist in the association of ApoE gene polymorphism with IS. The aim of this study was to investigate the ApoE gene polymorphism in relation to IS in the Guangxi Han populations and assess the risk of various ApoE genotypes associated with IS in Chinese populations. We conducted a case-control study involving a total of 166 IS cases and 192 healthy controls to investigate the association of ApoE gene polymorphism with IS in the Guangxi Han populations. Furthermore, we performed a meta-analysis to investigate whether the ApoE gene polymorphism is associated with IS in Chinese populations. There was no evidence for a significant association between ApoE gene polymorphism and IS in the Guangxi Han populations (É2/É2 vs. É3/É3: OR=1.25, 95% CI=0.08-20.17; É2/É3 vs. É3/É3: OR=1.49, 95% CI=0.79-2.79; É2/É4 vs. É3/É3: OR=1.25, 95% CI=0.17-9.00; É3/É4 vs. É3/É3: OR=1.10, 95% CI=0.60-2.04; É4/É4 vs. É3/É3: OR=2.50, 95% CI=0.22-27.87; allele É2 vs. allele É3: OR=1.39, 95% CI=0.80-2.44; allele É4 vs. allele É3: OR=1.16, 95% CI=0.68-1.98). In our meta-analysis, a significant association of ApoE gene polymorphism with IS was found in the genetic model of É2/É4 vs. É3/É3 (OR=2.04, 95% CI=1.45-2.85), É3/É4 vs. É3/É3 (OR=1.93, 95% CI=1.42-2.62), É4/É4 vs. É3/É3 (OR=3.41, 95% CI=2.17-5.34) and allele É4 vs. allele É3 (OR=2.34, 95% CI=1.91-2.86). However, no clear associations were found in the model of É2/É2 vs. É3/É3 (OR=1.56, 95% CI=0.90-2.71), É2/É3 vs. É3/É3 (OR=0.93, 95% CI=0.79-1.09) and allele É2 vs. allele É3 (OR=1.10, 95% CI=0.97-1.25). In conclusion, no association was found between ApoE gene polymorphism and IS in the Guangxi Han populations, while the results of the meta-analysis indicate that the ApoE mutation allele É4 increases the risk of IS in Chinese populations.