Year-end Sale % OFF 
Abstract
The genetic bases and disparate responses to radiotherapy are poorly understood, especially for cardiotoxicity resulting from treatment of thoracic tumors. Preclinical animal models such as the Dahl salt-sensitive (SS) rat can serve as a surrogate model for salt-sensitive low renin hypertension, common to African Americans, where aldosterone contributes to hypertension-related alterations of peripheral vascular and renal vascular function. Brown Norway (BN) rats, in comparison, are a normotensive control group, while consomic SSBN6 with substitution of rat chromosome 6 (homologous to human chromosome 14) on an SS background manifests cardioprotection and mitochondrial preservation to SS rats after injury. In this study, 2 groups from each of the 3 rat strains had their hearts irradiated (8 Gy X 5 fractions). One irradiated group was treated with the ACE-inhibitor lisinopril, and a separate group in each strain served as nonirradiated controls. Radiation reduced cardiac end diastolic volume by 9-11% and increased thickness of the interventricular septum (11-16%) and left ventricular posterior wall (14-15%) in all 3 strains (5-10 rats/group) after 120 days. Lisinopril mitigated the increase in posterior wall thickness. Mitochondrial function was measured by the Seahorse Cell Mitochondrial Stress test in peripheral blood mononuclear cells (PBMC) at 90 days. Radiation did not alter mitochondrial respiration in PBMC from BN or SSBN6. However, maximal mitochondrial respiration and spare capacity were reduced by radiation in PBMC from SS rats (p=0.016 and 0.002 respectively, 9-10 rats/group) and this effect was mitigated by lisinopril (p=0.04 and 0.023 respectively, 9-10 rats/group). Taken together, these results indicate injury to the heart by radiation in all 3 strains of rats, although the SS rats had greater susceptibility for mitochondrial dysfunction. Lisinopril mitigated injury independent of genetic background.
Highlights
Breast and lung cancer accounts for 28% of new cancer diagnoses in the United States, and 29% of cancer deaths [1]
Using the changes in echocardiogram parameters we aimed to identify functional changes that occurred in the hearts of irradiated SS, Brown Norway (BN) and SSBN6 rats, as well as to determine if the changes in mitochondrial bioenergetics in peripheral blood mononuclear cells (PBMC) could serve as a relatively non-invasive biomarker to predict genetically regulated, disparate responses to radiation
For the Brown Norway rats (BN rats) model, 10 rats were assigned to the control group, 10 rats received radiation, 5 rats received lisinopril and 5 rats received both radiation and lisinopril
Summary
Breast and lung cancer accounts for 28% of new cancer diagnoses in the United States, and 29% of cancer deaths [1]. Exposure of radiation to thoracic structures can cause a wide variety of acute symptoms and delayed toxicities, including cardiac injuries [3]. Radiation to the heart is often unavoidable when treating lung, breast, esophageal, and other thoracic malignancies. With the increasing role of radiation therapy in the contemporary treatment of cancer, patients that are long term survivors are at risk of cardiovascular injury and mortality [2, 3]. High-dose radiation exposure to the heart can cause cardiac dysfunction, developing months to decades following treatment [4, 5]. This includes injury to the cardiac tissues and vasculature, which can lead to complications such as pericarditis, coronary artery disease, ischemic heart disease, congestive heart failure, conduction defects and valvular dysfunction [6, 7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
