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Investigation of the Antihypertrophic and Antifibrotic Effects of Losartan in a Rat Model of Radiation-Induced Heart Disease.
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- المؤلفون: Kovács, Mónika Gabriella1 (AUTHOR) ; Kovács, Zsuzsanna Z. A.1 (AUTHOR) ; Varga, Zoltán2 (AUTHOR) ; Szűcs, Gergő1 (AUTHOR) ; Freiwan, Marah1 (AUTHOR) ; Farkas, Katalin3 (AUTHOR) ; Kővári, Bence4 (AUTHOR) ; Cserni, Gábor4 (AUTHOR) ; Kriston, András5,6,7 (AUTHOR) ; Kovács, Ferenc5,6,7 (AUTHOR) ; Horváth, Péter5,6,7 (AUTHOR) ; Földesi, Imre3 (AUTHOR) ; Csont, Tamás1 (AUTHOR) ; Kahán, Zsuzsanna2 (AUTHOR) ; Sárközy, Márta1 (AUTHOR)
- المصدر:
International Journal of Molecular Sciences. Dec2021, Vol. 22 Issue 23, p12963. 1p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
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. [ABSTRACT FROM AUTHOR]
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