RESUMEN
OBJECTIVE: Radiation-induced heart disease (RIHD) is a common sequela of thoracic irradiation. At the same time, nerve remodeling is involved in the progression of heart disease. However, the activation of the nerve remodeling related genes in radiation-induced heart disease is still lacking. METHODS: In this study, C57BL/J mice was anesthetized by intraperitoneal injection with pentobarbital sodium (2%, 40 mg/kg), and radiation was delivered using a cobalt-60 (60Co) teletherapy unit (Cirus). When the mice were anesthetized, none of them showed the signs of peritonitis, pain, or discomfort. The mice hearts were exposed to a γ-radiation field of 5 mm × 5 mm. The total dose of γ-radiation was 3 Gy/day for each animal for 5 consecutive days. The mice were executed by severed neck, and its limbs were weak. Quantitative Polymerase Chain Reaction (qPCR) and immunohistochemistry were used to explore the possible mechanism of arrhythmia in patients with RIHD. RESULTS: Our results demonstrated that Growth-Associated Protein 43 (GAP43) was increased significantly after radioactive heart injury compared with the control group. Moreover, the protein expression of Tyrosine hydroxylase (TH) and Choline acetyl-transferase (CHAT) was significantly decreased compared with the control group and gradually increased with time rend. The nerve growth factor (NGF) was remarkably increased after radiation-induced heart injury compared with the control group. Immunohistochemistry results indicated that the nerve growth factors GAP43 and NGF were significantly increased after radiation-induced heart injury. CONCLUSIONS: Chest radiotherapy could activate the neural modeling related genes in RIHD. This may provide a new treatment plan for the future treatment of heart problems caused by chest radiotherapy.
Asunto(s)
Cardiopatías/genética , Miocardio/metabolismo , Plasticidad Neuronal/genética , Plasticidad Neuronal/efectos de la radiación , Traumatismos Experimentales por Radiación/genética , Adulto , Anciano , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/genética , Biología Computacional , Femenino , Proteína GAP-43/genética , Rayos gamma/efectos adversos , Corazón/efectos de la radiación , Cardiopatías/etiología , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Modelos Neurológicos , Factor de Crecimiento Nervioso/genética , Traumatismos por Radiación/etiología , Traumatismos por Radiación/genética , Traumatismos Experimentales por Radiación/etiología , Radioterapia de Intensidad Modulada/efectos adversos , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
Long noncoding RNAs (lncRNAs) have been suggested to play indispensable roles in multiple heart diseases. However, the correlations between lncRNAs and atrial fibrillation (AF) are unclear. In this study, we performed comprehensive lncRNA profiling via high-throughput RNA sequencing analysis using non-AF and AF rabbit models. Based on a series of filtering pipelines and bioinformatics analyses, TCONS-00106987 was selected for further research. TCONS-00106987 levels were increased in the atria during AF. Moreover, the atrial effective refractory period was shortened and the AF inducibility was increased in vivo in response to lentiviral-mediated up-regulation of TCONS-00106987. TCONS-00106987 repression resulted in the opposite effects. Further studies indicated that TCONS-00106987 expression was positively correlated with the expression of the protein-coding gene KCNJ2. Luciferase reporter assays and whole-cell patch-clamp recording confirmed that TCONS-00106987 promoted electrical remodelling via endogenous competition with microRNA-26 (miR-26) to induce transcription of its target gene KCNJ2, thereby increasing inward-rectifier K+ current (IK1 ). In conclusion, our study reveals a pathogenic lncRNA-miRNA regulatory network specific to atrial electrical remodelling that offers potential therapeutic targets for AF.
Asunto(s)
Fibrilación Atrial/genética , Fibrilación Atrial/fisiopatología , Remodelación Atrial/genética , Regulación de la Expresión Génica , MicroARNs/metabolismo , Canales de Potasio de Rectificación Interna/genética , ARN Largo no Codificante/metabolismo , Animales , Secuencia de Bases , Unión Competitiva , Femenino , Perfilación de la Expresión Génica , Masculino , MicroARNs/genética , Canales de Potasio de Rectificación Interna/metabolismo , ARN Largo no Codificante/genética , Conejos , Regulación hacia Arriba/genéticaRESUMEN
Atrial fibrillation (AF) is an ectopic rhythm originating in the atrium. AF is the most common sustained cardiac arrhythmia in clinical practice and it is an enormous burden worldwide because of the high rates of morbidity, disability and mortality. Treatment of AF has become a hot spot in the field of cardiovascular medicine. Recently, increasing evidence and advancements in medical technology have helped us gain a better understanding of AF. As a result, management of AF has evolved in the past few years, so that we can better prevent and control AF. Current therapy for AF mainly includes drug therapy, catheter ablation, cryoballoon ablation, left atrial appendage closure and the maze procedure. The goal of this article is to update current treatment options for AF. We hope that this article will help deliver good care to AF patients based on the current state-of-the-art evidence.