Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease
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 c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12963 |
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| author | Mónika Gabriella Kovács 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 Márta Sárközy |
| author_facet | Mónika Gabriella Kovács 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 Márta Sárközy |
| author_sort | Mónika Gabriella Kovács |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:52:20Z |
| format | Article |
| id | doaj.art-73344728c8fc424f8272582801ccd5e0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:20Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-73344728c8fc424f8272582801ccd5e02023-11-23T02:31:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231296310.3390/ijms222312963Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart DiseaseMónika Gabriella Kovács0Zsuzsanna Z. A. Kovács1Zoltán Varga2Gergő Szűcs3Marah Freiwan4Katalin Farkas5Bence Kővári6Gábor Cserni7András Kriston8Ferenc Kovács9Péter Horváth10Imre Földesi11Tamás Csont12Zsuzsanna Kahán13Márta Sárközy14Interdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryInterdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryDepartment of Oncotherapy, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryInterdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryInterdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryDepartment of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryDepartment of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryDepartment of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungarySynthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungarySynthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungarySynthetic and Systems Biology Unit, Biological Research Centre, Eötvös Loránd Research Network, H-6726 Szeged, HungaryDepartment of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryInterdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryDepartment of Oncotherapy, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryInterdisciplinary Center of Excellence and MEDICS Research Group, Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, H-6720 Szeged, HungaryRadiation-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.https://www.mdpi.com/1422-0067/22/23/12963onco-cardiologyradiation-induced heart diseasediastolic dysfunctionleft ventricular hypertrophyfibrosisheart failure |
| spellingShingle | Mónika Gabriella Kovács 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 Márta Sárközy Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease International Journal of Molecular Sciences onco-cardiology radiation-induced heart disease diastolic dysfunction left ventricular hypertrophy fibrosis heart failure |
| title | Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease |
| title_full | Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease |
| title_fullStr | Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease |
| title_full_unstemmed | Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease |
| title_short | Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease |
| title_sort | investigation of the antihypertrophic and antifibrotic effects of losartan in a rat model of radiation induced heart disease |
| topic | onco-cardiology radiation-induced heart disease diastolic dysfunction left ventricular hypertrophy fibrosis heart failure |
| url | https://www.mdpi.com/1422-0067/22/23/12963 |
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