Lisinopril Mitigates Radiation-Induced Mitochondrial Defects in Rat Heart and Blood Cells. Front Oncol 2022;12:828177
Date
03/22/2022Pubmed ID
35311118Pubmed Central ID
PMC8924663DOI
10.3389/fonc.2022.828177Scopus ID
2-s2.0-85126780777 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
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.
Author List
Ortiz de Choudens S, Sparapani R, Narayanan J, Lohr N, Gao F, Fish BL, Zielonka M, Gasperetti T, Veley D, Beyer A, Olson J, Jacobs ER, Medhora MAuthors
Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of WisconsinJessica Olson PhD Director, Assistant Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Rodney Sparapani PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin
