New Insights into the Understanding of Mechanisms of Radiation-Induced Heart Disease

Wang, Kaixuan; Ye, Cong; Xu, Yang; Ma, Ping; Chen, Yan; Luo, Lan

doi:10.1007/s11864-022-01041-4

Cited by 15 publications

(7 citation statements)

References 126 publications

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“…Patients with thoracic cancer may suffer from RIHD within several years after radiotherapy, and this complication reduces the survival rate of antitumor treatment (Wang et al., 2023). Therefore, the treatment of RIHD is of great significance.…”

Section: Discussionmentioning

confidence: 99%

“…The early manifestations of RIHD are pericardial effusion or constriction, ischemia, heart valve disease, and arrhythmia. When RIHD develops into the late stage, the fibrosis of heart tissue can lead to systolic and diastolic dysfunction, affect the normal blood supply of myocardium in cardiac conduction system, and consequently cause ischemia and heart failure (Wang et al., 2023). The possible mechanisms of RIHD include inflammation and inflammatory cell infiltration, oxidative stress, increased microvascular superoxide production, endothelial injury, significant development of atherosclerotic lesions rich in macrophages, and mast cell proliferation (Livingston et al., 2020; Xu et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

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Protective effect of naringin against radiation‐induced heart disease in rats via Sirt1/NF‐κB signaling pathway and endoplasmic reticulum stress

Liu,

Zha,

et al. 2024

Chem Biol Drug Des

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This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation‐induced heart disease (RIHD) in rats. Rats were divided into four x‐ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin–eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis‐related proteins, endoplasmic reticulum stress‐related proteins, and Sirt1 (silent information regulator 1)/NF‐κB (nuclear factor kappa‐B) signaling pathway‐related proteins in cardiac tissues. Additionally, enzyme‐linked immunosorbent assay was utilized to detect the activities of pro‐inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR‐induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis‐related proteins (Col I, collagen type I; α‐SMA, α‐smooth muscle actin; and TGF‐β1, transforming growth factor‐beta 1) and endoplasmic reticulum stress‐related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro‐inflammatory cytokines [interleukin‐6, interleukin‐1β, and monocyte chemoattractant protein‐1 (MCP‐1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose‐dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF‐κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Protective effect of naringin against radiation‐induced heart disease in rats via Sirt1/NF‐κB signaling pathway and endoplasmic reticulum stress

Liu,

Zha,

et al. 2024

Chem Biol Drug Des

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“…This condition is characterized by cardiomyopathy, valvular disease, and atherosclerosis. Furthermore, prolonged radiation exposure can lead to myocardial fibrosis, which in turn can cause arrhythmias, myocardial ischemia, and ultimately cardiomyopathy [ 13 ]. Radiation pneumonitis is a potential side effect of radiotherapy for thoracic tumors.…”

Section: The Utilization Of Ionizing Radiation In Medicinementioning

confidence: 99%

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

Yu,

Xu,

Song

et al. 2023

J Transl Med

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Cancer remains the leading cause of death around the world. In cancer treatment, over 50% of cancer patients receive radiotherapy alone or in multimodal combinations with other therapies. One of the adverse consequences after radiation exposure is the occurrence of radiation-induced tissue fibrosis (RIF), which is characterized by the abnormal activation of myofibroblasts and the excessive accumulation of extracellular matrix. This phenotype can manifest in multiple organs, such as lung, skin, liver and kidney. In-depth studies on the mechanisms of radiation-induced fibrosis have shown that a variety of extracellular signals such as immune cells and abnormal release of cytokines, and intracellular signals such as cGAS/STING, oxidative stress response, metabolic reprogramming and proteasome pathway activation are involved in the activation of myofibroblasts. Tissue fibrosis is extremely harmful to patients' health and requires early diagnosis. In addition to traditional serum markers, histologic and imaging tests, the diagnostic potential of nuclear medicine techniques is emerging. Anti-inflammatory and antioxidant therapies are the traditional treatments for radiation-induced fibrosis. Recently, some promising therapeutic strategies have emerged, such as stem cell therapy and targeted therapies. However, incomplete knowledge of the mechanisms hinders the treatment of this disease. Here, we also highlight the potential mechanistic, diagnostic and therapeutic directions of radiation-induced fibrosis.

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“…Patients with cancer who undergo high‐dose thoracic radiotherapy may develop radiation‐induced heart disease (RIHD) [3], which is a heterogeneous, delayed, and potentially fatal adverse reaction to radiation that can cause damage to all structures of the heart. RIHD encompasses a spectrum of cardiac diseases, including radiation‐induced coronary artery disease (RICAD), heart failure (HF) with preserved/reduced ejection fraction (HFpEF/HFrEF), valvular heart disease (VHD), pericardial disease, cardiomyopathy, conduction abnormalities, myocardial fibrosis, peripheral vascular disease, arrhythmias, and sudden cardiac death [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Advances in multimodality imaging and the application of new cardiac imaging technologies for radiation‐induced heart disease

Du,

Lan,

Shen

et al. 2024

iRADIOLOGY

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Radiation‐induced heart disease (RIHD) is a heterogeneous, delayed, and potentially fatal adverse reaction to radiation that can damage all structures of the heart, including the pericardium, myocardium, coronary arteries, valves, and conduction system, leading to a series of diseases. Acute and chronic disease processes play a role in the development of RIHD, the onset times of which range from months to decades. However, the clinical manifestations of RIHD are usually insidious, overlap with several other diseases, and lack specificity. Cardiovascular imaging is essential for early diagnosis, follow‐up, and outcome assessment in patients with RIHD. This review first describes the pathogenesis and clinical manifestations of RIHD before providing an overview of the practical approaches and research advances in multimodal cardiovascular imaging in patients with RIHD, including echocardiography, cardiac magnetic resonance (CMR) and nuclear medicine, and cardiac computed tomography (CT). Then, the value of new cardiac imaging assessments for the early diagnosis of RIHD is described, particularly with relation to speckle‐tracking echocardiography, extracellular volume fraction assessment as a quantitative CMR technique, CMR myocardial strain assessment, positron emission tomography‐CT myocardial perfusion imaging, CT‐ECV, and CT strain assessment, amongst others. In addition, the advantages and disadvantages of each screening technique are compared with the aim of better guiding the follow‐up and diagnosis of subclinical RIHD and preventing cardiovascular events.

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New Insights into the Understanding of Mechanisms of Radiation-Induced Heart Disease

Cited by 15 publications

References 126 publications

Protective effect of naringin against radiation‐induced heart disease in rats via Sirt1/NF‐κB signaling pathway and endoplasmic reticulum stress

Protective effect of naringin against radiation‐induced heart disease in rats via Sirt1/NF‐κB signaling pathway and endoplasmic reticulum stress

Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

Advances in multimodality imaging and the application of new cardiac imaging technologies for radiation‐induced heart disease

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