0600270 - FGÚ 2025 RIV DE eng J - Článek v odborném periodiku
Gawrys, O. - Jíchová, Š. - Miklovič, M. - Husková, Z. - Kikerlová, S. - Sadowski, J. - Kollárová, P. - Lenčová-Popelová, O. - Hošková, L. - Imig, J. D. - Mazurová, Y. - Kolář, František - Melenovský, V. - Štěrba, M. - Červenka, L.
Characterization of a new model of chemotherapy-induced heart failure with reduced ejection fraction and nephrotic syndrome in Ren-2 transgenic rats.
Hypertension Research. Roč. 47, č. 11 (2024), s. 3126-3146. ISSN 0916-9636. E-ISSN 1348-4214
Grant CEP: GA MŠMT(CZ) LX22NPO5104
Institucionální podpora: RVO:67985823
Klíčová slova: doxorubicin * chemotherapy induced heart failure * Ren-2 transgenic hypertensive rat * experimental model of heart failure * NO/sGC/cGMP pathway
Obor OECD: Cardiac and Cardiovascular systems
Impakt faktor: 4.3, rok: 2023 ; AIS: 0.874, rok: 2023
Způsob publikování: Open access
Web výsledku:
https://doi.org/10.1038/s41440-024-01865-7DOI: https://doi.org/10.1038/s41440-024-01865-7

All anthracyclines, including doxorubicin (DOXO), the most common and still indispensable drug, exhibit cardiotoxicity with inherent risk of irreversible cardiomyopathy leading to heart failure with reduced ejection fraction (HFrEF). Current pharmacological strategies are clearly less effective for this type of HFrEF, hence an urgent need for new therapeutic approaches. The prerequisite for success is thorough understanding of pathophysiology of this HFrEF form, which requires an appropriate animal model of the disease. The aim of this study was to comprehensively characterise a novel model of HF with cardiorenal syndrome, i.e. DOXO-induced HFrEF with nephrotic syndrome, in which DOXO was administered to Ren-2 transgenic rats (TGR) via five intravenous injections in a cumulative dose of 10 mg/kg of body weight (BW). Our analysis included survival, echocardiography, as well as histological examination of the heart and kidneys, blood pressure, but also a broad spectrum of biomarkers to evaluate cardiac remodelling, fibrosis, apoptosis, oxidative stress and more. We have shown that the new model adequately mimics the cardiac remodelling described as “eccentric chamber atrophy” and myocardial damage typical for DOXO-related cardiotoxicity, without major damage of the peritoneum, lungs and liver. This pattern corresponds well to a clinical situation of cancer patients receiving anthracyclines, where HF develops with some delay after the anticancer therapy. Therefore, this study may serve as a comprehensive reference for all types of research on DOXO-related cardiotoxicity, proving especially useful in the search for new therapeutic strategies.
Trvalý link: https://hdl.handle.net/11104/0357615