The Role of Mitochondrial Dysfunction in Radiation-Induced Heart Disease: From Bench to Bedside

Abstract

Radiation is a key modality in the treatment of many cancers; however, it can also affect normal tissues adjacent to the tumor, leading to toxic effects. Radiation to the thoracic region, such as that received as part of treatment for breast and lung cancer, can result in incidental dose to the heart, leading to cardiac dysfunction, such as pericarditis, coronary artery disease, ischemic heart disease, conduction defects, and valvular dysfunction. The underlying mechanisms for these morbidities are currently being studied but are not entirely understood. There has been increasing focus on the role of radiation-induced mitochondrial dysfunction and the ensuing impact on various cardiac functions in both preclinical models and in humans. Cardiomyocyte mitochondria are critical to cardiac function, and mitochondria make up a substantial part of a cardiomyocyte's volume. Mitochondrial dysfunction can also alter other cell types in the heart. This review summarizes several factors related to radiation-induced mitochondrial dysfunction in cardiomyocytes and endothelial cells. These factors include mitochondrial DNA mutations, oxidative stress, alterations in various mitochondrial function-related transcription factors, and apoptosis. Through improved understanding of mitochondria-dependent mechanisms of radiation-induced heart dysfunction, potential therapeutic targets can be developed to assist in prevention and treatment of radiation-induced heart damage.

Mitochondrial dysfunction in cardiovascular disease: Current status of translational research/clinical and therapeutic implications

“…These deleterious effects may include mtDNA mutations, oxidative stress, alterations in various mitochondrial function-related transcription factors, and programmed cell death (apoptosis). 250 Hence, better T A B L E 4 Drugs producing mitochondrial dysfunction and cardiotoxicity | 301…”

“…In addition to drugs, radiation delivered to thorax, for example, for treatment of breast and lung cancer, lymphomas, and so forth, can affect the heart and also induce mitochondrial dysfunction in cardiomyocytes and endothelial cells. These deleterious effects may include mtDNA mutations, oxidative stress, alterations in various mitochondrial function‐related transcription factors, and programmed cell death (apoptosis) 250 . Hence, better understanding of mitochondria‐dependent mechanisms of radiation‐induced cardiac dysfunction, possible therapeutic targets can be devised to prevent and/or treat radiation‐induced cardiac injury.…”

Molecular mechanisms of melatonin’s protection against high-LET radiation: implications for space travel

“…Mitochondria possess a number of copies of the mitochondrial genome that is composed of a 16.5 kb circular DNA molecule (27). Mitochondria constitute a substantial part of the total cell volume (28). Accordingly, mitochondria are probably important targets of ionizing radiation (28).…”

“…Mitochondria constitute a substantial part of the total cell volume (28). Accordingly, mitochondria are probably important targets of ionizing radiation (28). Ionizing radiation is able to induce numerous lesions in the mitochondrial DNA (29,30).…”

“…Ionizing radiation is able to induce numerous lesions in the mitochondrial DNA (29,30). Ionizing radiation alters mitochondrial functions and induces production of ROS, leading to mitochondrial oxidative stress (28).…”