RESUMO
Myocardial infarction (MI) is one of the leading causes of high mortality worldwide. Long non-coding RNA myocardial infarction associated transcript (MIAT) and mitochondrial coupling factor 6 (CF6) aggravate MI. This study aimed to elucidate whether miR-203 interacted with MIAT and CF6 in MI. Results revealed that MIAT and CF6 expressions were upregulated and that miR-203 was downregulated in mouse myocardial tissues after MI, as well as in hypoxic mouse cardiomyocytes. The overexpression of MIAT in mouse cardiomyocytes raised CF6 expression, whereas the knockdown of MIAT had the opposite effect. Mechanistically, the luciferase reporter and RNA pull-down assays corroborated the binding between miR-203 and CF6 3'UTR and between miR-203 and MIAT. The simultaneous overexpression of miR-203 and MIAT restored the reduction of CF6 caused by miR-203 overexpression alone, and the overexpression of miR-203 diminished the percentage of infarct area and the apoptosis of cardiomyocytes in vivo. Our findings corroborate that overexpressing miR-203 alleviates MI via interacting with MIAT and CF6.
Assuntos
MicroRNAs/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Infarto do Miocárdio/genética , Fatores Acopladores da Fosforilação Oxidativa/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Fatores Acopladores da Fosforilação Oxidativa/genética , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: Myocardial infarction (MI) accompanied with abnormal sympathetic innervation, meanwhile, some studies have revealed the oxytocin (OT) and its receptor (OTR) have a relationship with MI and sympathetic system. It is assumed that OT has an close relationship with superior cervical ganglion (SCG), but the existence of oxytocin receptors in SCG has not been well clarified. OBJECTIVE: Our research aims to explore the expression of OTR in SCG in the setting of MI. METHODS AND RESULTS: MI was induced by coronary artery ligation. Rats were randomly assigned to 2 groups: control, MI. The expression of OTR was measured by Western blotting. Distribution of OTR in SCG was investigated by immunofluorescence. Retrograde tracing test revealed the sprouting of tyrosine hydroxylase (TH: the markers of sensory afferent fibers) from cardiac to SCG neurons. The double-immunofluorescence evidence showed that OTR was co-localized and concomitantly changed with TH and the retrograde neuronal labeling from the cardiac afferent nerves. By Western blotting, the protein of OTR in the MI group was higher than those of the control group. CONCLUSIONS: The expression of OTR in SCG after experimental myocardial infarction group was enhanced, suggesting the involvement of OTR in SCG may play a role in the transmission of sympathetic responses after MI.