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

20:09

PubMed articles on: Cardio-Oncology

Right ventricle toxicity in cancer treatment: a focused review on cardiac imaging

Future Cardiol. 2023 Oct 13. doi: 10.2217/fca-2022-0024. Online ahead of print.

ABSTRACT

Background: The right ventricle (RV) remains the 'forgotten chamber' in the clinical assessment of cancer therapy-related cardiac dysfunction (CTRCD). Aim: We aimed to review the role that various cardiac imaging modalities play in RV assessment as part of the integrative management of patients undergoing cancer therapy. Discussion: RV assessment remains challenging by traditional 2D echocardiography. In this review we discuss other parameters such as right atrial strain, and other echocardiographic modalities such as 3-dimensional and stress echocardiography. We also elaborate on the specific role that cardiac magnetic resonance imaging and equilibrium radionuclide angiocardiography can play in assessing the RV. Conclusion: Biventricular function should be monitored following chemotherapy for early detection of subclinical CTRCD and possible solitary RV changes.

PMID:37830360 | DOI:10.2217/fca-2022-0024

20:09

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.