Radiation-induced Heart Injury Research Articles

PTPMT1 protect cardiomyocytes from necroptosis induced by γ-ray irradiation through alleviate mitochondria injury.

Radiation-induced heart disease (RIHD) progresses over time and may manifest decades after the initial radiation exposure, which is associated with significant morbidity and mortality. The clinical benefit of radiotherapy is always counterbalanced by an increased risk of cardiovascular events in survivors. There is an urgent need to explore the effect and the underlying mechanism of radiation-induced heart injury. Mitochondrial damage widely occurs in irradiation-induced injury, and mitochondrial dysfunction contributes to necroptosis development. Experiments were performed using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and rat H9C2 cells to investigate the effect of mitochondrial injury on necroptosis in irradiated cardiomyocytes and to further elucidate the mechanism underlying radiation-induced heart disease and discover possible preventive targets. After γ-ray irradiation, the expression levels of necroptosis markers were increased, along with higher oxidative stress and mitochondrial injury. These effects could be abated by overexpression of PTEN-like mitochondrial phosphatase (PTPMT1). Inhibiting oxidative stress or increasing the expression of PTPMT1 could protect against radiation-induced mitochondrial injury and then decrease the necroptosis of cardiomyocytes. These results suggest that PTPMT1 may be a new target for the treatment of radiation-induced heart disease.

Evaluating the Mitigation Effect of Spirulina Against Radiation-Induced Heart Injury.

During a radiological or nuclear disaster, exposure to a high dose of ionizing radiation usually results in cardiovascular diseases such as heart failure, attack, and ischemia. The purpose of this study was to examine the mitigation effects of Spirulina in comparison to Metformin's. 25 male Wistar rats were randomly assigned to five groups (5 rats in each): for the control group, rats did not receive any intervention. In group 2, spirulina was administered orally to rats. In group 3, rats were irradiated to the chest region with 15 Gray(Gy) x-radiation. In groups 4 and 5, rats were irradiated in the same way as group 3. Forty-eight hours after irradiation, treatment with Spirulina and Metformin began. All rats were sacrificed after ten weeks, and their heart tissues were removed for histopathological and biochemical assays. Results showed an elevation in Malondialdehyde (MDA) and decreasing superoxide dismutase (SOD) activity. Moreover, pathological changes of radiation were irregularities in the arrangement of myofibrils, proliferation, migration of mononuclear cells, vacuolation of the cytoplasm, and congestion. Administration of spirulina enhanced the SOD activity while did not affect MDA level and pathological change in heart tissue. Despite spirulina, metformin had a considerable effect on pathological lesions and decreased the level of MDA. Reactive oxygen species (ROS) may be involved in the late effects of radiationinduced heart injury, and scavenging these particles may contribute to reduced radiation side effects. Based on these results, Spirulina had no effect on radiation-induced cardiac damage, while metformin did. Higher Spirulina doses given over a longer period of time will likely have a greater heart-mitigate effect.

Protective Role of Shenmai Injection on Radiation-Induced Heart Injury.

Radiation-induced heart injury (RIHI) limits the dose delivery of radiotherapy for thoracic cancer. Shenmai injection (SMI) is reported to have potential cytoprotective properties and is commonly used in cardiovascular diseases. So, we aimed to investigate the potential protective effects of SMI treatment on RIHI. In this study, we established the RIHI model using Sprague-Dawley rats and H9c2 cell line. In vivo, the biochemical assay was used to measure serum cardiac injury-related biomarkers and echocardiography to evaluate heart function. The pathological analysis was also applied to observe the myocardial structural changes. In vitro, we further measured the cell viability and reactive oxygen species (ROS) levels after irradiation with or without SMI treatment. Our data showed the administration of SMI reduced the level of serum cardiac injury biomarkers and ameliorated cardiac dysfunction after irradiation in rats. Pathological analysis revealed that SMI mitigated cardiac structural damage, fibrosis, and macrophage infiltration. Besides, treatment with SMI increased cell viability and decreased excess ROS production after irradiation in vitro. Taken together, our study demonstrated the protective role of SMI treatment on RIHI by inhibiting oxidative stress and decreasing structural remodeling.

Activation of Neural Modeling-Related Genes in the Heart of Mice after Gamma Irradiation.

Objective Radiation-induced heart disease (RIHD) is a common sequela of thoracic irradiation. At the same time, nerve remodeling is involved in the progression of heart disease. However, the activation of the nerve remodeling related genes in radiation-induced heart disease is still lacking. Methods In this study, C57BL/J mice was anesthetized by intraperitoneal injection with pentobarbital sodium (2%, 40 mg/kg), and radiation was delivered using a cobalt-60 (60Co) teletherapy unit (Cirus). When the mice were anesthetized, none of them showed the signs of peritonitis, pain, or discomfort. The mice hearts were exposed to a γ-radiation field of 5 mm × 5 mm. The total dose of γ-radiation was 3 Gy/day for each animal for 5 consecutive days. The mice were executed by severed neck, and its limbs were weak. Quantitative Polymerase Chain Reaction (qPCR) and immunohistochemistry were used to explore the possible mechanism of arrhythmia in patients with RIHD. Results Our results demonstrated that Growth-Associated Protein 43 (GAP43) was increased significantly after radioactive heart injury compared with the control group. Moreover, the protein expression of Tyrosine hydroxylase (TH) and Choline acetyl-transferase (CHAT) was significantly decreased compared with the control group and gradually increased with time rend. The nerve growth factor (NGF) was remarkably increased after radiation-induced heart injury compared with the control group. Immunohistochemistry results indicated that the nerve growth factors GAP43 and NGF were significantly increased after radiation-induced heart injury. Conclusions Chest radiotherapy could activate the neural modeling related genes in RIHD. This may provide a new treatment plan for the future treatment of heart problems caused by chest radiotherapy.

Effect of PD-1 Inhibitor on Cardiac Inflammatory Microenvironment and Radiation Induced Heart Injury

Effect of PD-1 Inhibitor on Cardiac Inflammatory Microenvironment and Radiation Induced Heart Injury

Multi-omic Analysis of Non-human Primate Heart after Partial-body Radiation with Minimal Bone Marrow Sparing.

High-dose radiation exposure results in hematopoietic and gastrointestinal acute radiation syndromes followed by delayed effects of acute radiation exposure, which encompasses multiple organs, including heart, kidney, and lung. Here we sought to further characterize the natural history of radiation-induced heart injury via determination of differential protein and metabolite expression in the heart. We quantitatively profiled the proteome and metabolome of left and right ventricle from non-human primates following 12 Gy partial body irradiation with 2.5% bone marrow sparing over a time period of 3 wk. Global proteome profiling identified more than 2,200 unique proteins, with 220 and 286 in the left and right ventricles, respectively, showing significant responses across at least three time points compared to baseline levels. High-throughput targeted metabolomics analyzed a total of 229 metabolites and metabolite combinations, with 18 and 22 in the left and right ventricles, respectively, showing significant responses compared to baseline levels. Bioinformatic analysis performed on metabolomic and proteomic data revealed pathways related to inflammation, energy metabolism, and myocardial remodeling were dysregulated. Additionally, we observed dysregulation of the retinoid homeostasis pathway, including significant post-radiation decreases in retinoic acid, an active metabolite of vitamin A. Significant differences between left and right ventricles in the pathology of radiation-induced injury were identified. This multi-omic study characterizes the natural history and molecular mechanisms of radiation-induced heart injury in NHP exposed to PBI with minimal bone marrow sparing.

Analysis of the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters related to right heart function in detecting acute radiation-induced right heart injury.

The aim of the present study was to investigate the value of parameters related to right heart function combined with N-terminal pro-B-type natriuretic peptide (NT-proBNP) in acute radiation-induced right heart injury. Seventy patients who received chest radiotherapy (RT) in the RT department of our hospital between September 2015 and March 2019 were included in the study. Of the included 70 patients, 19, 32, 4, and 15 had thoracic esophageal cancer, central lung cancer, thymoma, and left breast cancer, respectively. The Tei index, tricuspid annular displacement, right ventricular ejection fraction, and NT-proBNP of the 70 patients were measured 1 week before RT, at weeks 2 and 4 during RT, and 4 weeks after RT. Differences in the Tei index, the tricuspid annular displacement, and NT-proBNP were significant (P<0.01, P<0.05, and P<0.05, respectively). The Tei index significantly increased in the second week of RT. Tricuspid annular displacement decreased significantly 4 weeks after RT. NT-proBNP reached its peak value in the fourth week of RT. However, there was no significant difference in right ventricular ejection fraction (P>0.05). The Tei index of the right ventricle can be used as a sensitive indicator for the early detection of right heart injury after RT for thoracic tumors. Additionally, tricuspid annular displacement can be used as an index for the early detection of right ventricular damage after RT for thoracic tumors. However, right ventricular ejection fraction showed no significant change in the early stage of right heart damage after RT. Finally, it is important to consider NT-proBNP for the detection of acute radiation-induced heart injury. In acute radiation-induced right heart injury, the combined application of right ventricular Tei index, tricuspid annular displacement, and NT-proBNP is clinically relevant.

Observation of short-term clinical efficacy and adverse reactions with stereotactic radiotherapy in locally recurrent non-small cell lung cancer

Objective To investigate the short-term clinical efficacy and adverse reactions of stereotactic radiotherapy (SRT) in the treatment of locally recurrent non-small cell lung cancer (NSCLC). Methods Clinical data of 120 cases of recurrent NSCLC after radiotherapy admitted to our hospital from October 2009 to October 2015 were retrospectively analyzed. SRT was adopted for further radiotherapy. The prescription dose was 50% dose curve surrounding the target area. The total dose was 40-50 Gy, with a single dose of 4-5 Gy for 8-12 times. The chest CT was re-examined every 2 months after radiotherapy. The short-term clinical efficacy and adverse reactions were evaluated. The changes of Karnofsky performance score (KPS) and quality of life (QOL) were recorded before and after radiotherapy. Results One patient terminated the radiotherapy due to grade 3 acute radiation-induced pneumonia, 25 patients (21.0%) obtained complete remission (CR), 61 cases (51.3%) of partial remission (PR), 19 cases (16.0%) of stable disease (SD), 14 cases (11.8%) of progress disease (PD), 86 cases (72.3%) of objective remission rate (CR+ PR), and 105 cases (88.2%) of disease control (CR+ PR+ SD), respectively. Thirty-one patients experienced radiation-induced pneumonia, 23 cases of radiation-induced myelosuppression and 1 case of acute radiation-induced heart injury. All these adverse reactions were mitigated after symptomatic treatment. The KPS was significantly increased from 68.16±15.22 before SRT to 78.39±11.50 after SRT (P<0.05). The QOL was considerably elevated from 27.58±5.37 prior to SRT to 38.16±8.39 following SRT (P<0.01). Conclusion SRT is an efficacious and safe treatment of locally recurrent NSCLC, which yields controllable and tolerable adverse reactions and enhances the QOL of patients. Key words: Lung neoplasm, local recurrence/stereotactic radiotherapy; Short-term efficacy; Adverse reaction

Radiation-Induced Dual Oxidase Upregulation in Rat Heart Tissues: Protective Effect of Melatonin.

Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.

Two-dimensional speckle tracking imaging in assessing the left ventricular diastolic function of patients with esophageal carcinoma after radiotherapy

Objective To evaluate the early injury and dynamic changes of the left ventricular diastolic function of patients with esophageal carcinoma after radiotherapy by using two-dimensional speckle tracking imaging (2D-STI). Methods From 2017 to 2018, echocardiography examinations were performed in 39 patients with esophageal carcinoma before, during and after the first thoracic radiotherapy to measure the left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), early diastolic mitral flow velocity/early diastolic mitral annular peak velocity (E/e′), left atrial volume (LAV), 2D-STI parameters including the left ventricular global longitudinal strain (GLS), global systolic stain rate (GSRs), global early diastolic strain rate (GSRe), global late diastolic strain rate (GSRa) and E/GSRe ratio. According to the GLS of patients with esophageal carcinoma after radiotherapy (cumulative dose≥50 Gy), the patients were divided into good prognosis (n=23) and poor prognosis groups (n=16). The E/GSRe ratio was statistically compared between two groups. Results The E/e′and LAVI were increased significantly only after radiotherapy (both P<0.05), and LVEF was decreased significantly only after radiotherapy (P<0.05). The e′ tended to decline before, during and after radiotherapy (all P<0.05). GLS and GSRs were significantly decreased only after radiotherapy (both P<0.05), whereas GSRa was considerably decreased during radiotherapy (P<0.05). E/GSRe tended to increase (P<0.05). Compared with the good prognosis group, E/GSRe was significantly increased after radiotherapy in the poor prognosis group (P<0.05). Conclusions Diastolic dysfunction can occur in the early stage of radiation-induced heart injury. The global diastolic strain rate and E/GSRe obtained by 2D-STI can be used to assess the early left ventricular dysfunction. E/GSRe can be more sensitive to evaluate the clinical prognosis compared with the global diastolic strain rate. Key words: Two-dimensional speckle tracking imaging; Ventricular diastolic function; Esophageal neoplasm/radiotherapy

Research progress of radiation-induced heart injury—clinical

At present, the heart has become an important organ at risk during radiotherapy for thoracic, mediastinal and breast carcinoma. Heart is relatively sensitive to radiation because of its anatomical location and structure. Long-term survival of patients have been affected by cardiac adverse effect post-radiotherapy. In this paper, the progress of clinical manifestations, risk factors, screening methods, prevention and treatment of radiation-induced cardiac damage were reviewed as follows. Key words: Radiation-induced heart injury; Research progress

Evaluating the Radioprotective Effect of Curcumin on Rat's Heart Tissues.

Heart injury is one of the most important concerns after exposure to a high dose of radiation in chest cancer radiotherapy or whole body exposure to a radiation disaster. Studies have proposed that increased level of inflammatory and pro-fibrotic cytokines following radiotherapy or radiation events play a key role in the development of several side effects such as cardiovascular disorders. In the current study, we aimed to evaluate the expression of IL-4 and IL-13 cytokines as well as signaling pathways such as IL4Ra1, IL13Ra2, Duox1 and Duox2. In addition, we detected the possible protective effect of curcumin on the expression of these factors and infiltration of inflammatory cells. Twenty rats were divided into 4 groups including control; curcumin treated; radiation; and radiation plus curcumin. After 10 weeks, rats were sacrificed for evaluation of mentioned parameters. Results showed an increase in the level of IL-4 and all evaluated genes, as well as increased infiltration of lymphocytes and macrophages. Treatment with curcumin could attenuate these changes. Curcumin could reduce radiation-induced heart injury markers in rats.

Analysis of the evaluation errors of dose-volume parameters for left ventricular myocardium in esophageal cancer radiotherapy

Objective To evaluate the dynamic variation of the dose-volume parameters of the left ventricular myocardium following heart beat in radiotherapy for esophageal cancer. Methods The left ventricular myocardium of 22 patients was contoured on 20 phases (0%-95%) of electrocardiography (ECG) gated heart 4DCT images. The radiotherapy plan was designed on the simulation CT images, and then the dose distribution of radiotherapy plan was imported into MIM Maestro system and 4D dose-volume histogram (DVH) was reconstructed. The variations of position, volume and dice similarity coefficient (DSC) of the left ventricular myocardium were analyzed. The changing ranges of Dmean, V10, V20, V30 and V40 of the left ventricular myocardium during different phases were statistically compared. Results (1) The biggest displacement of the left ventricular myocardium was in Y axes. The maximum variation rate of volume and DSC of the left ventricular myocardium were (24.23±11.35)% and (184.33±128.61)% in different phases with statistical significance (both P<0.05). (2) The maximum variation rate of Dmean of the left ventricular myocardium was (87.05±38.34)% in different phases with the highest rate of 163.52% with statistical significance (P<0.05). (3) The maximum variation values of V10, V20, V30 and V40 of the left ventricular myocardium were (13.64±4.33)%, (12.84±4.55)%, (11.62±4.85)% and (3.63±2.56)% with statistical significance (all P<0.05). Conclusions The impact of heart beat on the dose-volume parameters of the left ventricular myocardium should be considered during esophageal cancer radiotherapy. Traditional static 3DCT-based assessment of the dose-volume parameters of the left ventricular myocardium can yield relatively large errors, which is probably reduces the prediction efficiency of the dose-volume parameters for radiation-induced heart injury. Key words: Left ventricular myocardium; Dose-volume parameter; Variation

Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat's Chest Irradiation.

Radiation-induced heart toxicity is one of the serious side effects after a radiation disaster or radiotherapy for patients with chest cancers, leading to a reduction in the quality of life of the patients. Evidence has shown that infiltration of inflammatory cells plays a key role in the development of functional damages to the heart via chronic upregulation of some pro-fibrotic and pro-inflammatory cytokines. These changes are associated with continuous free radical production and increased stiffness of heart muscle. IL-4 and IL-13 are two important pro-fibrotic cytokines which contribute to the side effects of ionizing radiation exposure. Recent studies have proposed that IL-4 through upregulation of DUOX2, and IL-13 via stimulation of DUOX1 gene expression, are involved in the development of radiation late effects. In the present study, we aimed to detect changes in the expression of these pathways following irradiation of rat’s heart. Furthermore, we evaluated the possible protective effect of metformin on the development of these abnormal changes. 20 male rats were divided into 4 groups (control, radiation, metformin treated, metformin + radiation). These rats were irradiated with 15 Gy 60Co gamma rays, and sacrificed after 10 weeks for evaluation of the changes in the expression of IL4R1, IL-13R2a, DUOX1 and DUOX2. In addition, the levels of IL-4 and IL-13 cytokines, as well as infiltration of macrophages and lymphocytes were detected. Results showed an upregulation of both DUOX1 and DUOX2 pathways in the presence of metformin, while the level of IL-13 did not show any significant change. This was associated with infiltration of macrophages and lymphocytes. Also, treatment with metformin could significantly attenuate accumulation of inflammatory cells, and upregulate these pathways. Therefore, suppression of dual oxidase genes by metformin may be a contributory factor to its protective effect.

Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury.

Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.

Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model.

Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR+BMSCs transplantation groups obtained at different time points. After irradiation, BMSC transplantation significantly enhanced the cardiac function in rats. By analyzing the expression of PPAR-α, PPAR-γ, TGF-β, IL-6, and IL-8, we found that BMSC transplantation alleviated radiation-induced myocardial fibrosis and decreased the inflammatory reaction. Furthermore, we found that expression of γ-H2AX, XRCC4, DNA ligase4, and TP53BP1, which are associated with DNA repair, was up-regulated, along with increased secretion of growth factors SDF-1, CXCR4, VEGF, and IGF in rat myocardium in the IRR+BMSCs transplantation groups compared with the IRR group. Thus, BMSC transplantation has the potential to improve RIHI via DNA repair and be a new therapeutic approach for patients with myocardial injury.

Establishment and validation of radiation-induced heart fibrosis on SD rat model

Objective To establish a Sprague-Dawley (SD) rat model of radiation-induced heart injury and myocardial fibrosis. Methods Using the small animal radiation research platform, 18-Gy radiation was given to the heart of male SD rats in a single fraction. At six months after radiation, heart structure and function were assessed by color Doppler ultrasound; heart injury and collagen fiber deposition were evaluated using HE staining and picrosirius red staining, respectively; heart collagen content was analyzed by hydroxyproline measurement. Results According to the color Doppler ultrasound assessment, the left ventricular posterior wall thickness during systole was significantly smaller in the radiation group than in the control group (0.22±0.01 vs. 0.25±0.05 cm, P=0.037). The results of picrosirius red staining showed that the proportions of fibrosis area in the right ventricle, interventricular septum, and left ventricle were significantly higher in the radiation group than in the control group ((2.99±1.29)% vs. (2.21±0.87)%, P=0.025; (2.53±1.27)% vs. (0.91±0.70)%, P=0.000; (2.45±1.98)% vs. (0.54±0.31)%, P=0.000). According to the measurement of hydroxyproline concentration, the radiation group had a significantly higher level of hydroxyproline than the control group (0.56±0.02 vs. 0.49±0.05 ug/mg, P=0.010), indicating severe heart collagen deposition after radiation. Conclusions At the end of model establishment, SD rats have obvious myocardial fibrosis and reduced left ventricular posterior wall thickness during systole, suggesting that a SD rat model of radiation-induced heart injury and myocardial fibrosis is successfully established. Key words: Radiation-induced myocardium fibrosis; Animal model; Rat

Atorvastatin Ameliorates Radiation-Induced Cardiac Fibrosis in Rats.

Radiation-induced heart injury is one of the major side effects of radiotherapy for thoracic malignancies. Previous studies have shown that radiotherapy induced myocardial fibrosis and intensified myocardial remodeling. In this study, we investigated whether atorvastatin could inhibit radiation-induced heart fibrosis in Sprague-Dawley rats, which were randomly divided into six groups: control; radiation only; and four treatment groups receiving atorvastatin plus radiation (E1, E2, E3 and E4). All rats, except the control group, received local heart irradiation in 7 daily fractions of 3 Gy for a total of 21 Gy. Rats in groups E1 (10 mg/kg/day) and E2 (20 mg/kg/day) received atorvastatin and radiation treatment until week 12 after exposure. Rats in groups E3 (10 mg/kg/day) and E4 (20 mg/kg/day) received atorvastatin treatment from 3 months before irradiation to week 12 after irradiation. The expressions of TGF-β1, Smad2, Smad3, fibronectin, ROCK I and p-Akt in heart tissues were evaluated using real-time PCR or Western blot analyses. Atorvastatin significantly reduced the expression of TGF-β1, Smad3/P-Smad3, ROCK I and p-Akt in rats of the E1-E4 groups and in a dose-dependent manner. Fibronectin exhibited a similar pattern of expression changes. In addition, echocardiography showed that atorvastatin treatment can inhibit the increase of left ventricular end-diastolic dimension, left ventricular end-systolic diameter and left ventricular posterior wall thickness, and prevent the decrease of ejection fraction and fraction shortening in E1-E4 groups compared with the radiation only group. This study demonstrated that radiation exposure increased the expression of fibronectin in cardiac fibroblasts and induced cardiac fibrosis through activation of the TGF-β1/Smad3, RhoA/ROCK, and PI3K/AKT signaling pathways. Statins ameliorated radiation-induced cardiac fibrosis in Sprague-Dawley rats. Our results suggest that atorvastatin is effective for the treatment of radiation-induced cardiac fibrosis, especially with longer and higher dose atorvastatin treatment, as demonstrated in experimental group E4.

Dose Volume Parameter Analysis on Late Radiation Induced Pericardial Effusion

Purpose/Objective(s)To evaluate the effect of dose-volume parameters on late radiation-induced Pericardial effusion in patients with thoracic carcinoma.Materials/MethodsA total of 49 patients with thoracic neoplasms who received irradiation were involved into the study. All patients underwent echocardiography and chest enhanced CT scan which were used to evaluate late radiation-induced pericardial effusion. Dose-volume parameters were analyzed to explore the influencing factors to it.ResultsDuring the observation period, late radiation-induced pericardial effusion was occurred in 14 patients (28.6%), 12 cases with small amount and 2 cases with middle effusion, there was no large pericardial effusion occurred. The studies showed that V30 and V35 of the heart were higher in late damage group than which in normal group (P=0.035 and P=0.038). Multivariate analysis showed that V30 of the heart was the independent influencing factor to late radiation-induced pericardial effusion (P=0.036). Receiver operator characteristic curve (ROC curve) analysis was used to find the appropriate threshold for V30, the area under ROC curve was 0.695, which meant the accuracy of the prediction was up to medium, the cut-off points were 33.0%. The late radiation-induced pericardial effusion incidence would be increased significantly when the V30 is over 33.0% (43.5% vs 15.4%). V30 prediction of sensitivity and specificity are 71.4%.ConclusionPericardial effusion is the common damage in late radiation-induced heart injury. The occurrence of that is associated with V30 and V35 receiving to the heart, and V30 is the independent influencing factor to late radiation-induced pericardial effusion. However, the final conclusion needs to sample observation. Purpose/Objective(s)To evaluate the effect of dose-volume parameters on late radiation-induced Pericardial effusion in patients with thoracic carcinoma. To evaluate the effect of dose-volume parameters on late radiation-induced Pericardial effusion in patients with thoracic carcinoma. Materials/MethodsA total of 49 patients with thoracic neoplasms who received irradiation were involved into the study. All patients underwent echocardiography and chest enhanced CT scan which were used to evaluate late radiation-induced pericardial effusion. Dose-volume parameters were analyzed to explore the influencing factors to it. A total of 49 patients with thoracic neoplasms who received irradiation were involved into the study. All patients underwent echocardiography and chest enhanced CT scan which were used to evaluate late radiation-induced pericardial effusion. Dose-volume parameters were analyzed to explore the influencing factors to it. ResultsDuring the observation period, late radiation-induced pericardial effusion was occurred in 14 patients (28.6%), 12 cases with small amount and 2 cases with middle effusion, there was no large pericardial effusion occurred. The studies showed that V30 and V35 of the heart were higher in late damage group than which in normal group (P=0.035 and P=0.038). Multivariate analysis showed that V30 of the heart was the independent influencing factor to late radiation-induced pericardial effusion (P=0.036). Receiver operator characteristic curve (ROC curve) analysis was used to find the appropriate threshold for V30, the area under ROC curve was 0.695, which meant the accuracy of the prediction was up to medium, the cut-off points were 33.0%. The late radiation-induced pericardial effusion incidence would be increased significantly when the V30 is over 33.0% (43.5% vs 15.4%). V30 prediction of sensitivity and specificity are 71.4%. During the observation period, late radiation-induced pericardial effusion was occurred in 14 patients (28.6%), 12 cases with small amount and 2 cases with middle effusion, there was no large pericardial effusion occurred. The studies showed that V30 and V35 of the heart were higher in late damage group than which in normal group (P=0.035 and P=0.038). Multivariate analysis showed that V30 of the heart was the independent influencing factor to late radiation-induced pericardial effusion (P=0.036). Receiver operator characteristic curve (ROC curve) analysis was used to find the appropriate threshold for V30, the area under ROC curve was 0.695, which meant the accuracy of the prediction was up to medium, the cut-off points were 33.0%. The late radiation-induced pericardial effusion incidence would be increased significantly when the V30 is over 33.0% (43.5% vs 15.4%). V30 prediction of sensitivity and specificity are 71.4%. ConclusionPericardial effusion is the common damage in late radiation-induced heart injury. The occurrence of that is associated with V30 and V35 receiving to the heart, and V30 is the independent influencing factor to late radiation-induced pericardial effusion. However, the final conclusion needs to sample observation. Pericardial effusion is the common damage in late radiation-induced heart injury. The occurrence of that is associated with V30 and V35 receiving to the heart, and V30 is the independent influencing factor to late radiation-induced pericardial effusion. However, the final conclusion needs to sample observation.

The lack of acute effect of low-to-moderate-dose ionising radiation on endothelial proteome

Epidemiological studies have shown that moderate and low radiation doses to the heart area may result in an increase in cardiovascular mortality. It has been suggested that cardiovascular endothelium could be one of the targets for the ionising radiation-induced heart injury. We have used human endothelial cells as an in vitro model to study immediate effects of ionising radiation on endothelium. Cells were exposed to low and moderate doses of γ-radiation, and short-term protein expression profiles were examined. Proteomics analysis did not show significant changes in the examined protein expression profiles after the γ-irradiation in any of the examined conditions. The molecular level cellular damage was verified by examining phosphorylation of tumour suppressor p53 binding protein 1, which was dose- and time-dependent. Further examination of cellular proteome and phosphoproteome, using more sensitive quantification and detection techniques, is warranted and might reveal changes, which were not detected in this study.