ABSTRACT

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in cancer patients treated with DOX. Angiotensin IV (Ang IV) has multiple protective effects against cardiovascular diseases, including diabetic cardiomyopathy and myocardial infarction, but its role in DOX-induced cardiotoxicity is currently unclear. In this study, we investigated the effects of Ang IV on DOX-induced cardiotoxicity.

METHODS: The viability of primary cardiomyocytes was measured by Cell Counting Kit-8 assays and Hoechst 33342/propidium iodide staining in vitro. ELISAs (serum cTnT and CK-MB) and echocardiography were performed to assess myocardial injury and cardiac function in vivo. Phalloidin staining, haematoxylin and eosin staining and wheat germ agglutinin staining were conducted to detect cardiomyocyte atrophy. We also performed C11 BODIPY staining, measured the levels of Ptgs2 and malondialdehyde and detected the concentrations of ferrous ions, glutathione and oxidized glutathione to indicate ferroptosis.

RESULTS: Ang IV not only attenuated DOX-induced atrophy and cardiomyocyte injury in vitro but also alleviated myocardial injury and improved cardiac function in DOX-treated mice in vivo. Moreover, Ang IV reversed DOX-induced downregulation of glutathione peroxidase 4 (GPX4) and inhibited ferroptosis both in vitro and in vivo. Knockdown of GPX4 by siRNA abolished the cardioprotective effects of Ang IV. Furthermore, Ang IV increased GPX4 levels and ameliorated ferroptosis in RAS-selective lethal 3-treated primary cardiomyocytes.

CONCLUSIONS: Ang IV ameliorates DOX-induced cardiotoxicity by upregulating GPX4 and inhibiting ferroptosis. Ang IV may be a promising candidate to protect against DOX-induced cardiotoxicity in the future.

PMID:37838222 | DOI:10.1016/j.taap.2023.116713

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PubMed articles on: Cardio-Oncology

Radiation Exposure of Cardiac Conduction Nodes During Breast Proton Therapy

Int J Part Ther. 2023 Mar 9;10(1):59-64. doi: 10.14338/IJPT-22-00038.1. eCollection 2023 Summer.

ABSTRACT

PURPOSE: The exposition of cardiac conduction system during breast radiation therapy has never been studied, despite the increasing use of intensity-modulated radiation therapy, which exposes larger volume to low-dose bath. We evaluated conduction node exposure during breast irradiation with volumetric modulated arc therapy and estimated the potential dosimetric benefit with intensity-modulated proton therapy.

MATERIALS AND METHODS: Atrioventricular (AVN) and sinoatrial (SAN) nodes were retrospectively delineated according to published guidelines on the simulation computed tomography scans of 12 breast cancer patients having undergone conserving surgery and adjuvant locoregional volumetric modulated arc therapy. Intensity-modulated proton therapy treatment was replanned on the simulation computed tomography scans for all breast cancer patients. Mean and maximum doses delivered to the SAN and the AVN were retrieved and compared. Correlation coefficients were calculated between doses to the SAN or the AVN and the whole heart.

RESULTS: Average mean doses delivered to the SAN and AVN were 2.8 and 2.3 Gy, respectively, for left-sided irradiation and 9.6 and 3.6 Gy, respectively, for right-sided irradiation. Average maximum doses to the SAN and AVN were 3.5 Gy and 2.8 Gy, respectively, for left-sided irradiation and 13.1 and 4.6 Gy, respectively, for right-sided irradiation. Intensity-modulated proton therapy significantly reduced mean and maximum doses to the SAN and AVN. Correlations between doses to the SAN or AVN and whole heart were usually significant.

CONCLUSION: SAN and AVN can be substantially exposed during breast volumetric modulated arc therapy, especially for right-sided irradiation. Cardiotoxicity studies evaluating conduction node exposure might define dose constraints and criteria for additional cardiac-sparing techniques, such as respiratory techniques or proton therapy, which could benefit patients with underlying rhythmic or conduction disorders.

PMID:37823017 | PMC:PMC10563662 | DOI:10.14338/IJPT-22-00038.1

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PubMed articles on: Cardio-Oncology

Tailored to a Woman's Heart: Gender Cardio-Oncology Across the Lifespan

Curr Cardiol Rep. 2023 Oct 11. doi: 10.1007/s11886-023-01967-7. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Females outnumber males among long-term cancer survivors, primarily as a result of the prevalence of breast cancer. Late cardiovascular effects of cancer develop over several decades, which for many women, may overlap with reproductive and lifecycle events. Thus, women require longitudinal cardio-oncology care that anticipates and responds to their evolving cardiovascular risk.

RECENT FINDINGS: Women may experience greater cardiotoxicity from cancer treatments compared to men and a range of treatment-associated hormonal changes that increase cardiometabolic risk. Biological changes at critical life stages, including menarche, pregnancy, and menopause, put female cancer patients and survivors at a unique risk of cardiovascular disease. Women also face distinct psychosocial and physical barriers to accessing cardiovascular care. We describe the need for a lifespan-based approach to cardio-oncology for women. Cardio-oncology care tailored to women should rigorously consider cancer treatment/outcomes and concurrent reproductive/hormonal changes, which collectively shape quality of life and cardiovascular outcomes.

PMID:37819431 | DOI:10.1007/s11886-023-01967-7

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PubMed articles on: Cardio-Oncology

Inhibiting mir-34a-5p regulates doxorubicin-induced autophagy disorder and alleviates myocardial pyroptosis by targeting Sirt3-AMPK pathway

Biomed Pharmacother. 2023 Oct 6;168:115654. doi: 10.1016/j.biopha.2023.115654. Online ahead of print.

ABSTRACT

Doxorubicin (DOX) is a commonly used chemotherapy drug widely applied in various cancers such as breast cancer, leukemia, and sarcomas. However, its usage is limited by cardiotoxicity. Additionally, the cardiac toxicity of DOX accumulates with dose and duration, making it imperative to identify therapeutic targets for DOX-induced cardiomyopathy (DIC). It has been reported that miRNAs are involved in the progression of DIC. Mir-34a-5p has been identified as an early diagnostic marker for DIC. While studies have shown the involvement of mir-34a-5p in DIC apoptosis, it has not been validated in animal models, nor has the potential improvement of DIC by inhibiting mir-34a-5p been confirmed. Autophagy and pyroptosis are key factors in the development of DIC and can serve as therapeutic targets for its treatment. In this study, we found that mir-34a-5p was upregulated in the heart after DOX treatment and that the inhibition of mir-34-5p reduced autophagy and pyroptosis in DIC. We also found that the inhibition of mir-34a-5p inhibited pyroptosis by regulating autophagy and reducing mitochondrial reactive oxygen species. Moreover, we identified Sirtuin3 (Sirt3) as a target gene of mir-34a-5p using a double-luciferase reporter assay. overexpression Sirt3 reduced pyroptosis by alleviating autophagy. Our research findings suggest that inhibiting mir-34a-5p has a beneficial role in alleviating autophagy and pyroptosis in DIC. This provides therapeutic prospects for treating DIC.

PMID:37806095 | DOI:10.1016/j.biopha.2023.115654

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PubMed articles on: Cardio-Oncology

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial

BMC Cancer. 2023 Oct 14;23(1):980. doi: 10.1186/s12885-023-11489-8.