Radiation-induced cardiovascular disease: an overlooked role for DNA methylation?

Abstract

Radiotherapy in cancer treatment involves the use of ionizing radiation for cancer cell killing. Although radiotherapy has shown significant improvements on cancer recurrence and mortality, several radiation-induced adverse effects have been documented. Of these adverse effects, radiation-induced cardiovascular disease (CVD) is particularly prominent among patients receiving mediastinal radiotherapy, such as breast cancer and Hodgkin's lymphoma patients. A number of mechanisms of radiation-induced CVD pathogenesis have been proposed such as endothelial inflammatory activation, premature endothelial senescence, increased ROS and mitochondrial dysfunction. However, current research seems to point to a so-far unexamined and potentially novel involvement of epigenetics in radiation-induced CVD pathogenesis. Firstly, epigenetic mechanisms have been implicated in CVD pathophysiology. In addition, several studies have shown that ionizing radiation can cause epigenetic modifications, especially DNA methylation alterations. As a result, this review aims to provide a summary of the current literature linking DNA methylation to radiation-induced CVD and thereby explore DNA methylation as a possible contributor to radiation-induced CVD pathogenesis.

Association Between Radiotherapy and Death From Cardiovascular Disease Among Patients With Cancer: A Large Population‐Based Cohort Study

“…Radiotherapy‐induced CVD is also affected by the dose of cardiac radiation. 32 , 34 Therefore, radiotherapy‐induced CVD is a complex and modifiable pathophysiological process.…”

DNA Methylation Alterations in Fractionally Irradiated Rats and Breast Cancer Patients Receiving Radiotherapy

“…Thoracic radiotherapy has been shown to increase the risk of cardiac toxicity in cancer patients [1][2][3]. Despite the current radiation-sparing techniques, which limit cardiac exposure, radiation-induced cardiovascular disease (RICVD) is still a primary clinical concern that manifests mainly as coronary heart disease, remaining asymptomatic until 10 to 15 years after radiotherapy [4]. However, a 6% decrease in global longitudinal strain (GLS), an early sign of subclinical left ventricular dysfunction, has been reported in breast cancer (BC) patients as early as 6 months after radiotherapy [5,6].…”

“…Interestingly, radiation has also been shown to affect DNA methylation. Both radiation-induced global hypomethylation, as well as gene-specific hypermethylation, have been reported [4,16,17]. However, the contribution of DNA methylation in X-irradiation-induced cardiac toxicity is underexplored.…”

Modulators of radiation-induced cardiopulmonary toxicities for non-small cell lung cancer: Integrated cytokines, single nucleotide variants, and HBP systems imaging

“…The process of fibroblast cells changes to myofibroblast cells due to ROS-mediated DNA damage. The change the integrity of the genome could lead to cell cycle arrest, apoptosis, mutation and other effects (35).…”

“…NF-κB regulates DNA transcription and protein complexes engage in various cellular oxidative stress responses. The change the integrity of the genome could lead to cell cycle arrest, apoptosis, mutation and other effects ( 35 ).…”