The role of connexin proteins and their channels in radiation-induced atherosclerosis

Radiotherapy is an effective treatment for breast cancer and other thoracic tumors. However, while high-energy radiotherapy treatment successfully kills cancer cells, radiation exposure of the heart and large arteries cannot always be avoided, resulting in secondary cardiovascular disease in cancer survivors. Radiation-induced changes in the cardiac vasculature may thereby lead to coronary artery atherosclerosis, which is a major cardiovascular complication nowadays in thoracic radiotherapy-treated patients. The underlying biological and molecular mechanisms of radiation-induced atherosclerosis are complex and still not fully understood, resulting in potentially improper radiation protection. Ionizing radiation (IR) exposure may damage the vascular endothelium by inducing DNA damage, oxidative stress, premature cellular senescence, cell death and inflammation, which act to promote the atherosclerotic process. Intercellular communication mediated by connexin (Cx)-based gap junctions and hemichannels may modulate IR-induced responses and thereby the atherosclerotic process. However, the role of endothelial Cxs and their channels in atherosclerotic development after IR exposure is still poorly defined. A better understanding of the underlying biological pathways involved in secondary cardiovascular toxicity after radiotherapy would facilitate the development of effective strategies that prevent or mitigate these adverse effects. Here, we review the possible roles of intercellular Cx driven signaling and communication in radiation-induced atherosclerosis.

Automated summary

Radiation therapy is effective in treating breast cancer and other thoracic tumors, but can lead to secondary cardiovascular diseases due to radiation exposure of the heart and large arteries. Radiation-induced coronary artery atherosclerosis is a major cardiovascular complication in thoracic radiotherapy-treated patients, with complex biological and molecular mechanisms that are not fully understood. Ionizing radiation exposure can damage the vascular endothelium, leading to atherosclerosis through various mechanisms such as DNA damage, oxidative stress, cellular senescence, and inflammation.