Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors

Radiation‐induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure...

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Main Authors: Chunan Zhao, Shuai Xu, Yanru Yang, Xing Shen, Jingjing Wang, Shuang Xing, Zuyin Yu
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.040937
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author Chunan Zhao
Shuai Xu
Yanru Yang
Xing Shen
Jingjing Wang
Shuang Xing
Zuyin Yu
author_facet Chunan Zhao
Shuai Xu
Yanru Yang
Xing Shen
Jingjing Wang
Shuang Xing
Zuyin Yu
author_sort Chunan Zhao
collection DOAJ
description Radiation‐induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation‐induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation‐induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL‐6 (interleukin‐6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.
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spelling doaj-art-28e727672f2b4bb4a4541437c49b70a82025-08-20T03:07:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-05-01141010.1161/JAHA.124.040937Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of TumorsChunan Zhao0Shuai Xu1Yanru Yang2Xing Shen3Jingjing Wang4Shuang Xing5Zuyin Yu6Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing ChinaDepartment of Cardiology Chinese PLA General Hospital Beijing ChinaDepartment of Cardiology Chinese PLA General Hospital Beijing ChinaDepartment of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing ChinaDepartment of Cardiology Chinese PLA General Hospital Beijing ChinaDepartment of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing ChinaDepartment of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing ChinaRadiation‐induced heart disease (RIHD) is a prevalent cardiovascular complication of radiation therapy, with coronary heart disease being the most common manifestation. Clinical presentations of RIHD vary and may include conduction abnormalities, ischemic heart disease, cardiomyopathy, heart failure, and valvular damage. Even low doses of radiation significantly increase the risk of cardiovascular disease, often associated with severe stenosis detected via angiography. Radiation‐induced damage to the cardiac endothelium triggers inflammatory responses and oxidative stress, which contribute to the progression of atherosclerosis. This study explores how radiation activates multiple signaling pathways through the generation of reactive oxygen species, resulting in vascular endothelial damage, cellular senescence, inflammatory responses, and DNA damage. It further examines the impact of radiation on vascular integrity and tight junction proteins, leading to increased vascular permeability and infiltration by inflammatory cells. From a clinical perspective, we emphasize the challenges posed by the coexistence of tumors in many patients with RIHD, as tumors complicate the microenvironment and may have mutually reinforcing interactions with radiation‐induced damage. We also discuss various therapeutic strategies, including novel approaches targeting cellular senescence and immune responses, with a focus on the potential use of navitoclax and IL‐6 (interleukin‐6) inhibitors to prevent irreversible cardiomyocyte fibrosis and ongoing vascular damage. In conclusion, RIHD is a multifaceted disease involving complex biological processes and signaling pathways. Early intervention and targeted therapies are crucial for improving patient outcomes. Future research should prioritize uncovering the molecular mechanisms of RIHD and developing more effective therapeutic strategies.https://www.ahajournals.org/doi/10.1161/JAHA.124.040937endothelial damageimmunotherapyradiation‐induced coronary heart diseaseradiation‐induced heart disease (RIHD)senescence‐associated secretory phenotype (SASP)
spellingShingle Chunan Zhao
Shuai Xu
Yanru Yang
Xing Shen
Jingjing Wang
Shuang Xing
Zuyin Yu
Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
endothelial damage
immunotherapy
radiation‐induced coronary heart disease
radiation‐induced heart disease (RIHD)
senescence‐associated secretory phenotype (SASP)
title Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
title_full Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
title_fullStr Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
title_full_unstemmed Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
title_short Intersection of Cardio‐Oncology: An Overview of Radiation‐Induced Heart Disease in the Context of Tumors
title_sort intersection of cardio oncology an overview of radiation induced heart disease in the context of tumors
topic endothelial damage
immunotherapy
radiation‐induced coronary heart disease
radiation‐induced heart disease (RIHD)
senescence‐associated secretory phenotype (SASP)
url https://www.ahajournals.org/doi/10.1161/JAHA.124.040937
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