Activation of Neural Modeling-Related Genes in the Heart of Mice after Gamma Irradiation.

Zhiyong Liu,Ximin Wang,Jing Liu,Jiandong Zhang,Juanjuan Du,Dan Hu,Donglu Liu,Yinglong Hou,Osamah Ibrahim Khalaf

doi:10.1155/2021/8522417

Abstract

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.

Highlights

Radiotherapy is an indispensable part of multidisciplinary treatment of malignancies
Studies have shown that nerve growth factor (NGF) synthesized and released by damaged myocardium and inflammatory tissue plays an important role in nerve remodeling
These results demonstrated that radiation heart injury will lead to changes in nerve-related factors

Summary

Introduction

Radiotherapy is an indispensable part of multidisciplinary treatment of malignancies. It has previously been proposed that approximately 52.3% of all oncological patients should receive radiation during the course of their illness [1]. Normal tissue injury associated with radiotherapy is clinical issues of multidisciplinary treatment for malignancies. Radiation-induced heart diseases (RIHDs) have become one of the major causes of nonneoplastic death in patients receiving thoracic irradiation, especially with old technique of radiotherapy, in patients with classical Hodgkin’s lymphoma [2,3,4] and early-stage breast cancer [5,6,7]. The application of more sophisticated techniques has greatly decreased the dose delivered to the whole heart and its substructures. Cardiac toxicity remains a major concern when balancing target coverage and minimizing cardiac dose in delivering radiotherapy to thoracic tumors. The cardiovascular complications of radiotherapy are generally coronary artery disease, pericardial disease, cardiomyopathy/myocardial fibrosis, valvular disease, and arrhythmia [9]

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Conclusion