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Article

Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease

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Interdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
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Department of Oncotherapy, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
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Department of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
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Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, Hungary
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Synthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, Hungary
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Single-Cell Technologies Ltd., H-6726 Szeged, Hungary
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Institute for Molecular Medicine Finland (FIMM), University of Helsinki, FIN-00014 Helsinki, Finland
*
Authors to whom correspondence should be addressed.
These authors contributed to the work equally.
Academic Editors: Francesco Fedele and Paul J. Mather
Int. J. Mol. Sci. 2021, 22(23), 12963; https://doi.org/10.3390/ijms222312963
Received: 31 October 2021 / Revised: 25 November 2021 / Accepted: 26 November 2021 / Published: 30 November 2021
(This article belongs to the Special Issue Heart Failure: From Molecular Basis to Therapy 2.0)
Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial. We aimed at investigating the effects of losartan in a rat model of RIHD. Male Sprague-Dawley rats were studied in three groups: (1) control, (2) radiotherapy (RT) only, (3) RT treated with losartan (per os 10 mg/kg/day), and were followed for 1, 3, or 15 weeks. At 15 weeks post-irradiation, losartan alleviated the echocardiographic and histological signs of LVH and fibrosis and reduced the overexpression of chymase, connective tissue growth factor, and transforming growth factor-beta in the myocardium measured by qPCR; likewise, the level of the SMAD2/3 protein determined by Western blot decreased. In both RT groups, the pro-survival phospho-AKT/AKT and the phospho-ERK1,2/ERK1,2 ratios were increased at week 15. The antiremodeling effects of losartan seem to be associated with the repression of chymase and several elements of the TGF-β/SMAD signaling pathway in our RIHD model. View Full-Text
Keywords: onco-cardiology; radiation-induced heart disease; diastolic dysfunction; left ventricular hypertrophy; fibrosis; heart failure; angiotensin-II receptor blocker (ARB); losartan; chymase; TGF-β/SMAD signaling pathway onco-cardiology; radiation-induced heart disease; diastolic dysfunction; left ventricular hypertrophy; fibrosis; heart failure; angiotensin-II receptor blocker (ARB); losartan; chymase; TGF-β/SMAD signaling pathway
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MDPI and ACS Style

Kovács, M.G.; Kovács, Z.Z.A.; Varga, Z.; Szűcs, G.; Freiwan, M.; Farkas, K.; Kővári, B.; Cserni, G.; Kriston, A.; Kovács, F.; Horváth, P.; Földesi, I.; Csont, T.; Kahán, Z.; Sárközy, M. Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease. Int. J. Mol. Sci. 2021, 22, 12963. https://doi.org/10.3390/ijms222312963

AMA Style

Kovács MG, Kovács ZZA, Varga Z, Szűcs G, Freiwan M, Farkas K, Kővári B, Cserni G, Kriston A, Kovács F, Horváth P, Földesi I, Csont T, Kahán Z, Sárközy M. Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease. International Journal of Molecular Sciences. 2021; 22(23):12963. https://doi.org/10.3390/ijms222312963

Chicago/Turabian Style

Kovács, Mónika G., Zsuzsanna Z.A. Kovács, Zoltán Varga, Gergő Szűcs, Marah Freiwan, Katalin Farkas, Bence Kővári, Gábor Cserni, András Kriston, Ferenc Kovács, Péter Horváth, Imre Földesi, Tamás Csont, Zsuzsanna Kahán, and Márta Sárközy. 2021. "Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease" International Journal of Molecular Sciences 22, no. 23: 12963. https://doi.org/10.3390/ijms222312963

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