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Int Immunopharmacol ; 111: 109158, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35987147

ABSTRACT

Selenium, reported as an important medium for maintaining the body's homeostasis, acts to have multiple bioeffects including anti-inflammatory, anti-oxidant and anti-apoptosis effects. However, its role in heart failure still remains unclear. In this study, we explored the effects of selenium on heart failure and its possible mechanism. The heart failure models were induced by aortic banding and isoproterenol. H&E, TUNEL and PSR staining were performed to detect the degree of cardiomyocyte hypertrophy, apoptosis rates and heart fibrosis, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect different mRNA levels, and western blot was applied to assess the expressions of relative proteins. Immunofluorescence staining was used to evaluate α-SMA density. We first found that treatment of selenium alleviated heart fibrosis and the development of heart failure but not cardiomyocyte cross sectional areas. Besides, selenium improved heart levels of superoxide dismutase2 (SOD2), glutathione peroxidase (Gpx) and glutathione (GSH) and the activity of SOD, accompanied by decreased apoptosis rate. In addition, our in vitro study has shown that selenium reduced mRNA levels of collagen Ⅰ and collagen III, expressions of a-SMA, p-AKT/AKT and p-GSK-3ß/ GSK-3ß, apoptosis rates and reactive oxygen species (ROS) levels in H9C2 cardio-myoblasts treated with TGF-ß1. Moreover, the level of Sirt1 was found to be up-regulated by selenium which effects were weakened after the administration of small interfering RNA (siRNA)-Sirt1 or EX527 (inhibitor of Sirt1). Our current results have demonstrated that the protective effects of selenium on heart hypertrophy is through the regulation of Sirt1 and AKT/GSK-3ß pathway.


Subject(s)
Heart Failure , Selenium , Animals , Collagen/metabolism , Fibrosis , Glycogen Synthase Kinase 3 beta/metabolism , Heart Failure/drug therapy , Myocytes, Cardiac/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Selenium/pharmacology , Selenium/therapeutic use , Signal Transduction , Sirtuin 1/metabolism
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