RESUMEN
It is formerly conducted that long non-coding RNA growth arrest-specific 5 (GAS5) is involved in the process of coronary atherosclerosis (AS). The regulatory effects of GAS5 on the microRNA (miR)-194-3p/thioredoxin-interacting protein (TXNIP) axis in AS have been insufficiently explored yet. Thereafter, this work is started from GAS5/miR-194-3p/TXNIP axis in AS. AS rats were modeled to obtain their coronary vascular tissues and endothelial cells (ECs), in which GAS5, miR-194-3p, and TXNIP expression were tested. ECs were identified by immunohistochemistry. The mechanism among GAS5, miR-194-3p, and TXNIP was determined. ECs were transfected with inhibited GAS5 or overexpressed miR-194-3p to decipher their functions in proliferation and apoptosis of ECs in AS. Raised GAS5 and TXNIP and degraded miR-194-3p expression levels exhibited in AS. GAS5 bound to miR-194-3p while miR-194-3p targeted TXNIP. Depleting GAS5 or restoring miR-194-3p enhanced proliferation and depressed apoptosis of ECs in AS. This work clearly manifests that inhibited GAS5 facilitates the growth of ECs through miR-194-3p-targeted TXNIP in AS, consolidating the basal reference to the curing for AS.
Asunto(s)
Proteínas de Ciclo Celular/biosíntesis , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/patología , MicroARNs/biosíntesis , ARN Largo no Codificante/biosíntesis , Animales , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Masculino , ARN Largo no Codificante/antagonistas & inhibidores , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Recently, the function of microRNAs (miRNAs) has been clarified in human diseases, we aimed to identify the role of miR-185 in myocardial infarction (MI). METHODS: Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which the exosomes were extracted. MI mice models were established by coronary artery ligation and injected with transfected BMSCs. The echocardiographic and ventricle indicators, and hemodynamics of mice were measured. Moreover, the ultrastructure and apoptosis of cardiomyocytes were determined, and expression of miR-185, suppressor of cytokine signaling 2 (SOCS2), collagens, and apoptotic proteins in myocardial tissues were evaluated. RESULTS: MiR-185 was poorly expressed in myocardial tissues of MI mice. BMSCs-Exo could shuttle miR-185 to promote cardiac function and attenuate myocardial injury of myocardial tissues in MI mice, and also could protect cardiomyocytes from apoptosis in MI mice by reducing the expression of SOCS2. SOCS2 was determined to be the direct target gene of miR-185. Overexpressed SOCS2 could block the cardioprotective effect of BMSCs-derived exosomal miR-185 in MI mice. CONCLUSION: We have found in this study that BMSCs-derived exosomal miR-185 could repress ventricular remolding of MI mice by inhibiting SOCS2. This study may provide new method for MI treatment.
Asunto(s)
Células Madre Mesenquimatosas/metabolismo , MicroARNs/metabolismo , Infarto del Miocardio/genética , Proteínas Supresoras de la Señalización de Citocinas/genética , Remodelación Ventricular/genética , Animales , Apoptosis/genética , Apoptosis/inmunología , Línea Celular , Modelos Animales de Enfermedad , Ecocardiografía , Exosomas/metabolismo , Exosomas/trasplante , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/inmunología , Ventrículos Cardíacos/patología , Humanos , Masculino , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Ratones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/inmunología , Infarto del Miocardio/terapia , Miocitos Cardíacos , Remodelación Ventricular/inmunologíaRESUMEN
BACKGROUND: This study was aimed to unveil micro RNA (miRNA) expression profiles in myocardial ischemia-reperfusion (MI/R) rats and explore whether and how dysregulated miRNAs were involved in the initiation and progression of MI/R in a calcium-dependent manner. METHOD AND RESULTS: Rat model of MI/R was established and cardiomyocytes isolated from neonatal rats cardiomyocytes were induced. Both miRNA and messenger RNA expression profiles were analyzed by Microarray. Quantitative reverse-transcription polymerase chain reaction, immunoblotting, bioinformatics analysis, dual-luciferase reporter gene assay, hematoxylin and eosin, Evans blue, and triphenyl tetrazolium chloride were also used in this study. Serum concentrations of myocardial enzymes (phosphocreatine kinase [CK], creatine kinase [CK-MB], lactate dehydrogenase [LDH]), cardiomyocytes loadage of Ca2+ , as well as the expression level of inositol 1,4,5-trisphosphate receptors (IP3R) and sarcoplasmic reticulum Ca2+ -ATPase 2a (SERCA2a) were measured, respectively. Effects of upregulation or downregulation of miR-202-5p or Trpv2 on these indicators were investigated in vivo and in vitro. In MI/R rats and hypoxia/reoxygenation-induced NCMs, miR-202-5p was downregulated, while Trpv2 was upregulated. Trpv2 was a promising target of miR-202-5p and negatively regulated by miR-202-5p. Upregulation of miR-202-5p or downregulation of Trpv2 significantly reduced the serum concentration of myocardial enzymes, as well as cardiomyocyte-produced reactive oxygen species, but inhibition of miR-202-5p or overexpression of Trpv2 brought the worsening situation for these indicators. Besides, upregulation of miR-202-5p upregulation or downregulation of Trpv2 also inhibited Ca2+ overload in cardiomyocytes, accompanied with the increase of SERCA2a and suppression of IP3R. The reduced damage degree and infarct size in myocardial tissue were contrarily worsened by miR-202-5p inhibitor. CONCLUSION: Overexpression of miR-202-5p or downregulation of its downstream Trpv2 presented the cardioprotective effects to MI/R rats.