Radiation oncologists' perspectives on reducing radiation-induced heart disease in early breast cancer

Mahdavi, Hoda

doi:10.1016/j.currproblcancer.2019.100509

Cited by 9 publications

(7 citation statements)

References 30 publications

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“…The American Heart Association has reported the existence of several overlapping risk factors for BC and CVDs, such as smoking, poor dietary habits, sedentary lifestyle, diabetes, and obesity [10]. The risk of CVD death in BC patients may also be increased by the cardiotoxic effects of treatment, such as receiving radiation and chemotherapy [11][12][13]. The most common cardiotoxic effect during BC treatment is left ventricular dysfunction with or without heart failure [13].…”

Section: Introductionmentioning

confidence: 99%

“…The risk of CVD death in BC patients may also be increased by the cardiotoxic effects of treatment, such as receiving radiation and chemotherapy [11][12][13]. The most common cardiotoxic effect during BC treatment is left ventricular dysfunction with or without heart failure [13]. Especially in elderly patients, the threat of death from CVDs is higher than that of BC itself [14].…”

Section: Introductionmentioning

confidence: 99%

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Competing risk analysis of cardiovascular death in Breast Cancer: Evidence from SEER-Medicaid

Shun-de

Liu

et al. 2023

Preprint

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Purpose: The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with breast cancer (BC). Methods: Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. Standardized mortality rate (SMRs) for cardiovascular disease (CVD) were calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Results: Overall, 399,014 BC patients were included from the SEER database, of whom 7023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients (SMR = 4.84, 95% CI: 4.72–4.95). Multivariate competing risk regression analysis revealed age, sex, race, American Joint Committee on Cancer stage, year of diagnosis, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, BC subtype, surgery, and median household income as independent predictors of CVM in BC patients. Conclusions: Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors will improve overall survival of BC patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Competing risk analysis of cardiovascular death in Breast Cancer: Evidence from SEER-Medicaid

Shun-de

Liu

et al. 2023

Preprint

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“…Large clinical studies have found that the long-term survival of patients who have undergone thoracic radiotherapy is impaired by radiation-induced heart damage (RIHD) [3][4][5]. RIHD is mainly observed many years after patients receive thoracic radiotherapy, manifesting as coronary artery disease, ischemic heart disease, pericarditis, conduction defects, and valvular dysfunction [6][7][8]. RIHD can impact prognosis and increase cardiac mortality and has become a challenge in clinical practice [9,10].…”

Section: Introductionmentioning

confidence: 99%

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Zeng

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective Ionizing radiation (IR) causes cardiac senescence, which eventually manifests as radiation-induced heart damage (RIHD). This study is aimed at exploring the mechanisms underlying IR-induced senescence using acetylation proteomics. Methods Irradiated mouse hearts and H9C2 cells were harvested for senescence detection. Acetylation proteomics was used to investigate alterations in lysine acetylation. Atp5f1c acetylation after IR was verified using coimmunoprecipitation (Co-IP). Atp5f1c lysine 55 site acetylation (Atp5f1c K55-Ac) point mutation plasmids were used to evaluate the influence of Atp5f1c K55-Ac on energy metabolism and cellular senescence. Deacetylation inhibitors, plasmids, and siRNA transfection were used to determine the mechanism of Atp5f1c K55-Ac regulation. Results The mice showed cardiomyocyte and cardiac aging phenotypes after IR. We identified 90 lysine acetylation sites from 70 protein alterations in the heart in response to IR. Hyperacetylated proteins are primarily involved in energy metabolism. Among them, Atp5f1c was hyperacetylated, as confirmed by Co-IP. Atp5f1c K55-Ac decreased ATP enzyme activity and synthesis. Atp5f1c K55 acetylation induced cardiomyocyte senescence, and Sirt4 and Sirt5 regulated Atp5f1c K55 deacetylation. Conclusion Our findings reveal a mechanism of RIHD through which Atp5f1c K55-Ac leads to cardiac aging and Sirt4 or Sirt5 modulates Atp5f1c acetylation. Therefore, the regulation of Atp5f1c K55-Ac might be a potential target for the treatment of RIHD.

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“…Unfortunately, patients obtain therapeutic bene ts from radiotherapy while ionizing radiation may bring normal organ complications to patients at the same time [2,3]. Radiation-induced heart damage (RIHD) is mainly observed after radiotherapy for malignant chest tumors, especially left breast cancer and Hodgkin's lymphoma with high de nitive cure rates [4,5]. RIHD is mainly characterized by coronary artery disease, ischemic heart disease, pericarditis, conduction defects, and valvular dysfunction and so on [6,7].…”

Section: Introductionmentioning

confidence: 99%

Acetylation of ATP5f1c mediates cardiomyocyte senescence via metabolic dysfunction in radiation induced heart damage

Zeng

et al. 2022

Preprint

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Objective: Ionizing radiation (IR) causes heart senescence, which eventually manifests as radiation-induced heart damage (RIHD). Energy metabolism of cardiomyocytes is involved in senescence. This study attempts to explore radiation-induced senescence mechanisms through TMT-labeled proteomics.Methods: Echocardiography, senescence-associated secretory phenotype (SASP), telomere length and P21 expression were conducted to detect IR induced senescence. Total protein acetylation of irradiated heart apex and H9C2 cells was discovered by Western blotting compared with the control. To further investigate lysine acetylation alterations in irradiated heart proteins, proteomics of lysine acetylation was performed. Acetylated level of Atp5f1c was verified by Co-IP. The plasmids of the acetylated-mimicking Atp5f1c mutant (K55Q), deacetylated-mimicking Atp5f1c mutant (K55R) and WT were constructed and used for to transfect H9C2 cells to prove that acetylated Atp5f1c participated in energy metabolism and senescence. Deacetylation inhibitors, plasmid transfection and Co-IP were used to determine the mechanism of upstream regulation of Atp5f1c K55-Ac.Results: LVEF was decreased, SASP was elevated, telomere length was shortened and P21was overexpressed after IR. In addition, the total protein acetylation level significantly increased, and 69 proteins, including 90 sites, showed a lysine acetylation response to irradiation. The majority of the hyperacetylated proteins were related to energy metabolism. The ATP synthase γ subunit was hyperacetylated at the 55th lysine site and led to decreased ATP enzyme activity and synthesis decreased. Atp5f1c K55-Ac induced H9C2 metabolic dysfunction and senescence. Sirt4 and Sitr5, deacetylase inhibitors, mediated Atp5f1c K55-Ac deacetylation. Conclusion: IR induced cardiomyocyte senescence and energy metabolism disorder. Atp5f1c K55-ac, which is modulated by Sirt4 or Sirt5, might be a potential molecular target underlying RIHD.

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Radiation oncologists' perspectives on reducing radiation-induced heart disease in early breast cancer

Cited by 9 publications

References 30 publications

Competing risk analysis of cardiovascular death in Breast Cancer: Evidence from SEER-Medicaid

Competing risk analysis of cardiovascular death in Breast Cancer: Evidence from SEER-Medicaid

Acetylation of Atp5f1c Mediates Cardiomyocyte Senescence via Metabolic Dysfunction in Radiation-Induced Heart Damage

Acetylation of ATP5f1c mediates cardiomyocyte senescence via metabolic dysfunction in radiation induced heart damage

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