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心脏肿瘤学交叉领域:肿瘤背景下放射性心脏病概述

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

作者信息

Zhao Chunan, Xu Shuai, Yang Yanru, Shen Xing, Wang Jingjing, Xing Shuang, Yu Zuyin

机构信息

Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology Beijing Institute of Radiation Medicine Beijing China.

Department of Cardiology Chinese PLA General Hospital Beijing China.

出版信息

J Am Heart Assoc. 2025 May 20;14(10):e040937. doi: 10.1161/JAHA.124.040937. Epub 2025 May 13.

DOI:10.1161/JAHA.124.040937
PMID:40357679
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12184584/
Abstract

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.

摘要

放射性心脏病(RIHD)是放射治疗常见的心血管并发症,其中冠心病是最常见的表现形式。RIHD的临床表现各异,可能包括传导异常、缺血性心脏病、心肌病、心力衰竭和瓣膜损害。即使是低剂量辐射也会显著增加心血管疾病风险,常伴有血管造影检测到的严重狭窄。辐射对心脏内皮的损伤引发炎症反应和氧化应激,这会促进动脉粥样硬化的进展。本研究探讨辐射如何通过产生活性氧激活多种信号通路,导致血管内皮损伤、细胞衰老、炎症反应和DNA损伤。研究还进一步考察辐射对血管完整性和紧密连接蛋白的影响,导致血管通透性增加和炎症细胞浸润。从临床角度看,我们强调许多RIHD患者中肿瘤共存带来的挑战,因为肿瘤会使微环境复杂化,且可能与辐射诱导的损伤产生相互促进作用。我们还讨论了各种治疗策略,包括针对细胞衰老和免疫反应的新方法,重点关注维托克洛克斯和白细胞介素-6(IL-6)抑制剂预防不可逆心肌细胞纤维化和持续血管损伤的潜在用途。总之,RIHD是一种涉及复杂生物学过程和信号通路的多方面疾病。早期干预和靶向治疗对改善患者预后至关重要。未来研究应优先揭示RIHD的分子机制并开发更有效的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c23/12184584/800816e02566/JAH3-14-e040937-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c23/12184584/8756b47ba619/JAH3-14-e040937-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c23/12184584/bba6d8b652dc/JAH3-14-e040937-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c23/12184584/46770c8b1f7d/JAH3-14-e040937-g001.jpg
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本文引用的文献

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STING directly interacts with PAR to promote apoptosis upon acute ionizing radiation-mediated DNA damage.在急性电离辐射介导的DNA损伤后,STING直接与PAR相互作用以促进细胞凋亡。
Cell Death Differ. 2025 Feb 12. doi: 10.1038/s41418-025-01457-z.
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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.利用肿瘤微环境:通过调节上皮-间质转化实现靶向癌症治疗
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