# Research progress in the prevention and treatment of radiation-induced heart disease

## TL;DR

Radiotherapy for chest cancers can cause heart disease, but antioxidants and anti-inflammatory drugs may help prevent or treat it.

## Contribution

This review summarizes the mechanisms of radiation-induced heart disease and evaluates potential therapeutic strategies.

## Key findings

- Ionizing radiation causes oxidative stress and activates pathways like NF-κB and TGF-β1, leading to heart damage.
- Statins, ACEIs, and natural antioxidants show promise in mitigating radiation-induced heart disease in preclinical studies.
- Clinical validation is needed to confirm the effectiveness of these therapies for radiation-induced heart disease.

## Abstract

Radiotherapy (RT) is a cornerstone treatment for thoracic malignancies, but is associated with an increased risk of radiation-induced heart disease (RIHD), a major cause of long-term morbidity and mortality in cancer survivors. Ionizing radiation directly damages cellular components (proteins, lipids, and DNA), disrupts the mitochondrial electron transport chain, and activates enzymes such as NADPH oxidases, this leads to excessive production and accumulation of reactive oxygen species (ROS). Oxidative stress triggers the pro-inflammatory NF-κB pathway, pro-oxidative MAPK branch of IGF-1 signaling, and the pro-fibrotic TGF-β1 pathway. These cascades promote chronic inflammation, endothelial dysfunction, and microvascular damage, leading to myocardial fibrosis and dysfunction. Antioxidant and anti-inflammatory therapies represent a promising approach for the clinical management of RIHD. Preclinical evidence has suggested that statins, angiotensin-converting enzyme inhibitors (ACEIs), and natural antioxidants such as sodium Tanshinone IIA sulfonate mitigate RIHD by scavenging ROS, reducing inflammation, and inhibiting fibrosis. However, further clinical validation of these drugs is required for RIHD. This review highlights the current research status of the known pathophysiological mechanisms of RIHD, and the various treatment strategies used for its prevention and treatment.

Flowchart illustrating the biochemical pathways of TGF-beta signaling, ROS generation, and their effects on collagen synthesis and oxidative stress. The chart shows interactions between SMAD2/3, NF-kB, IGF-1, PI3K, and enzymes like NADPH oxidase. The pathway leads to conditions such as cardiomyopathies, heart valve diseases, arrhythmias, coronary heart disease, and pericardial diseases. External factors like statins and radiation are also depicted.