Discovery and confirmation of crucial genes associated with radiation-induced heart disease

<b>Objective:</b> Radiotherapy is an essential method for treating cancerous tumors, and the resultant radiation-induced heart disease (RIHD) has emerged as the leading non-cancerous cause of mortality among cancer survivors. However, the mechanisms of RIHD are still unknown, and specific biomarkers and effective treatment methods are needing to be found. <b>Methods:</b> Fourteen male C57BL/6J mice, each 8 weeks old, were randomly assigned into two groups: an experimental group (n = 7) and a control group (n = 7). The test group underwent irradiation with 30 Gy of ⁶⁰Co γ-rays. To assess the acute and chronic damage to the myocardium caused by radiation, heart tissues were collected at one day and six weeks after irradiation for transcriptome sequencing, and H&E staining and immunohistochemical staining were done, respectively. <b>Results:</b> One day after radiation, the myocardial tissue showed a significant amount of inflammatory cell infiltration. Following a period of six weeks, there was an increase in hypertrophic cardiomyocytes and myocardial fibrosis. Additionally, we identified several genes (<i>Cmpk2, Ifit3, Dhx58, Slc2a1, and Thbs1</i>) that were strongly associated with RIHD. The expression of these genes in heart tissue was significantly upregulated after six weeks of radiation. Findings from the GO functional and KEGG pathway enrichment analysis, along with the hub gene function analysis, indicate that the mechanism behind RIHD might be linked to systemic inflammation and mitochondrial dysfunction. <b>Conclusion:</b> Acute radiation myocardial injury is characterized by inflammation, while chronic radiation myocardial injury is characterized by myocardial fibrosis. RIHD is linked to <i>Cmpk2</i>, <i>Ifit3</i>, <i>Dhx58</i>, <i>Slc2a1</i>, and <i>Thbs1</i> genes through a mechanism that may cause systemic inflammation and mitochondrial dysfunction.