Radiation-induced heart disease: a review of classification, mechanism and prevention

Wang, Heru; Wei, Jinlong; Zheng, Qinsi; Meng, Lingbin; Xin, Ying; Yin, Xia; Jiang, Xin

doi:10.7150/ijbs.35460

Cited by 161 publications

(157 citation statements)

References 126 publications

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“…In homeostasis, ROS facilitate cellular functions, including immune responses, signal transduction and apoptosis. ROS can be neutralized by antioxidants when their concentrations are in excess (29). If this highly regulated process is disrupted, increased production or decreased removal of ROS can lead to cellular and DNA damage (29).…”

Section: Mitochondria and Oxidative Stressmentioning

confidence: 99%

“…Mitochondria are critical for some methods of programmed cell death, or apoptosis. For the intrinsic pathway, the inner and outer mitochondrial membranes must be permeabilized to release apoptotic factors, such as cytochrome c. The Bcl-2/Bax family of proteins help regulate and stabilize the membranes and govern the predilection for mitochondrial membrane permeabilization (29,67). Once Bax is activated, it translocates from the cytoplasm to the mitochondrial membrane, where it can induce membrane permeability transition (MPT).…”

Section: Mitochondria and Apoptosismentioning

confidence: 99%

“…Radiation may also cause mitochondrial-mediated apoptosis due to the close association between the endoplasmic reticulum and mitochondria. When cardiomyocytes are irradiated, the endoplasmic reticulum releases a flux of excess calcium ions (Ca 2+ ) that facilitate permeabilization of mitochondria (29). Animal studies have shown increased levels of the Bax/Bcl2 ratio expression following irradiation.…”

Section: Mitochondria and Apoptosismentioning

confidence: 99%

“…Endothelial cell functions that can be altered by radiation include Ca 2+ regulation, apoptosis and oxidative stress signaling. Radiationinduced release of Ca 2+ from the endoplasmic reticulum leads to increased mitochondrial Ca 2+ uptake, yielding membrane swelling and release of apoptotic factors (29). However, Ca 2+ plays numerous roles in signaling pathways and intracellular functions that theoretically may be affected by radiation (e.g., inner membrane calcium uniporter, mitochondrial Ca 2+ activation of dehydrogenase enzymes and ATP synthase and TNF-α-induced inflammation).…”

Section: Endothelial Cell Mitochondriamentioning

confidence: 99%

“…An additional cause is macrovascular and microvascular injury, developed in a multifactorial manner by endothelial cell damage and adhesion, and activation of inflammatory and atherosclerotic responses (1,6,(23)(24)(25)(26)(27)(28). Signaling pathways, including apoptosis and mitochondrial dysfunction, have also been linked to RIHD (29,30). This review will focus on the role of radiationinduced mitochondrial dysfunction in RIHD.…”

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confidence: 99%

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

Livingston

Schlaak

Puckett

et al. 2020

Front. Cardiovasc. Med.

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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.

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Section: Mitochondria and Oxidative Stressmentioning

confidence: 99%

Section: Mitochondria and Apoptosismentioning

confidence: 99%

Section: Mitochondria and Apoptosismentioning

confidence: 99%

Section: Endothelial Cell Mitochondriamentioning

confidence: 99%

mentioning

confidence: 99%

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

Livingston

Schlaak

Puckett

et al. 2020

Front. Cardiovasc. Med.

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Association of Breast Cancer Irradiation With Cardiac Toxic Effects

et al. 2021

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IMPORTANCETo promptly recognize and manage cardiovascular (CV) risk factors before, during, and after cancer treatment, decreasing the risk of cancer therapy-related cardiac dysfunction is crucial. After recent advances in breast cancer treatment, mortality rates from cancer have decreased, and the prevalence of survivors with a potentially higher CV disease risk has increased. Cardiovascular risks might be associated with the multimodal approach, including systemic therapies and breast radiotherapy (RT).OBSERVATIONS The heart disease risk seems to be higher in patients with tumors in the left breast, when other classic CV risk factors are present, and when adjunctive anthracycline-based chemotherapy is administered, suggesting a synergistic association. Respiratory control as well as modern RT techniques and their possible further refinement may decrease the prevalence and severity of radiation-induced heart disease. Several pharmacological cardioprevention strategies for decreasing cardiac toxic effects have been identified in several guidelines. However, further research is needed to ascertain the feasibility of these strategies in routine practice.CONCLUSIONS AND RELEVANCE This review found that evidence-based recommendations are lacking on the modalities for and intensity of heart disease screening, surveillance of patients after RT, and treatment of these patients. A multidisciplinary and multimodal approach is crucial to guide optimal management.

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Relative thoracic changes from supine to upright patient position: A proton collaborative group study

Marano,

Kissick,

Underwood

et al. 2023

J Applied Clin Med Phys

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This study presents position changes of a few radiotherapy‐relevant thoracic organs between upright and typical supine patient orientations. Using tools in a commercial treatment planning system (TPS), key anatomical distances were measured for four‐dimensional CT data sets and analyzed for the two patient orientations. The uncertainty was calculated as the 95% confidence interval (CI) on the relative difference for each of the four analyzed changes for upright relative to supine, as follows: the distance of the bottom of the heart to the top of the sternum, it changed +2.6% or +4 mm (95% CI [+0.30%,+4.9%]); the distance of the center of the C3 vertebra to the backrest, it changed +29% (95% CI [+22%,+36%]); the contoured left and right lungs increased their volumes respectively: +17% (95% CI [+12%,+21%]) for the left, and +9.9% (95% CI [+4.1%,+16%]); and lastly, the distance from the top of the sternum to the top of the liver, but its uncertainty far exceeded the average change by a factor of two. This last result is therefore inconclusive, the others show that with 95% confidence that a change in internal positions is observed for lung volumes and heart position that could be important for upright treatments.

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Radiation-induced heart disease: a review of classification, mechanism and prevention

Cited by 161 publications

References 126 publications

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

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

Association of Breast Cancer Irradiation With Cardiac Toxic Effects

Relative thoracic changes from supine to upright patient position: A proton collaborative group study

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