TY - JOUR
T1 - The Role of Mitochondrial Dysfunction in Radiation-Induced Heart Disease
T2 - From Bench to Bedside
AU - Livingston, Katie
AU - Schlaak, Rachel A.
AU - Puckett, Lindsay L.
AU - Bergom, Carmen
N1 - Funding Information:
We apologize to the authors whose work was not cited due to space limitations. Funding. This work was supported by the Medical College of Wisconsin (MCW) Cancer Center and the Dr. Nancy Sobczak Fund for Breast Cancer (CB). Support was also received from NIH/NHLBI 1R01HL147884 (CB), the Mary Kay Foundation Grant No. 017-29 (CB), a Susan G. Komen Grant #CCR17483233 (CB), and the Michael H. Keelan, Jr., MD, Research Foundation Grant and the Cardiovascular Center at the Medical College of Wisconsin (CB).
Publisher Copyright:
© Copyright © 2020 Livingston, Schlaak, Puckett and Bergom.
PY - 2020/2/21
Y1 - 2020/2/21
N2 - 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.
AB - 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.
KW - apoptosis
KW - cardiomyocyte
KW - endothelial cell
KW - mitochondria
KW - oxidative stress
KW - radiation
KW - radiation-adverse effects
KW - radiation-induced cardiovascular toxicity
UR - http://www.scopus.com/inward/record.url?scp=85091195823&partnerID=8YFLogxK
U2 - 10.3389/fcvm.2020.00020
DO - 10.3389/fcvm.2020.00020
M3 - Review article
C2 - 32154269
AN - SCOPUS:85091195823
SN - 2297-055X
VL - 7
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 20
ER -