BACKGROUND: To further explore the role of PPARγ in QL treatment, ISO-induced mice model and following methods were established. METHODS: Cardiac remodeling on mice model was induced by isoproterenol (ISO) infusion or saline infusion as control for two weeks then divided into 4 groups, after that divided in 5 different treatment methods to investigate the role of PPARγ in QL therapy. Echocardiography and Masson's trichrome staining were respectively used to determine cardiac function and fibrosis. Immunoblotting was applied to evaluate the expression levels of proliferator-activated receptor-γ (PPARγ), Bax, Bcl, phospho-Akt (Ser473), Akt, phospho-P38 and P38, phosphor-ERK and ERK. RESULTS: QL treatment improved left ventricular function, decreased apoptosis, and prevented myocardial fibrosis at the same time. Meanwhile, the PPARγ level was elevated with QL treatment in ISO-injected mice hearts. Inhibition of PPARγ activity blocked the protective effects of QL, while the activator of PPARγ did not provide additional benefit. Specifically, the results indicated a decline in PPARγ in ISO-infused mice and QL decreased the toxicity of ISO by improving the level of PPARγ. CONCLUSIONS: Our study demonstrated that QL treatment provided cardioprotection against ISO-induced cardiac remodeling by improving PPARγ level, which could be as the potential therapeutic target in reversing cardiac remodeling and heart failure.
BACKGROUND: To further explore the role of PPARγ in QL treatment, ISO-induced mice model and following methods were established. METHODS:Cardiac remodeling on mice model was induced by isoproterenol (ISO) infusion or saline infusion as control for two weeks then divided into 4 groups, after that divided in 5 different treatment methods to investigate the role of PPARγ in QL therapy. Echocardiography and Masson's trichrome staining were respectively used to determine cardiac function and fibrosis. Immunoblotting was applied to evaluate the expression levels of proliferator-activated receptor-γ (PPARγ), Bax, Bcl, phospho-Akt (Ser473), Akt, phospho-P38 and P38, phosphor-ERK and ERK. RESULTS: QL treatment improved left ventricular function, decreased apoptosis, and prevented myocardial fibrosis at the same time. Meanwhile, the PPARγ level was elevated with QL treatment in ISO-injected mice hearts. Inhibition of PPARγ activity blocked the protective effects of QL, while the activator of PPARγ did not provide additional benefit. Specifically, the results indicated a decline in PPARγ in ISO-infused mice and QL decreased the toxicity of ISO by improving the level of PPARγ. CONCLUSIONS: Our study demonstrated that QL treatment provided cardioprotection against ISO-induced cardiac remodeling by improving PPARγ level, which could be as the potential therapeutic target in reversing cardiac remodeling and heart failure.
Authors: Steven R Houser; Kenneth B Margulies; Anne M Murphy; Francis G Spinale; Gary S Francis; Sumanth D Prabhu; Howard A Rockman; David A Kass; Jeffery D Molkentin; Mark A Sussman; Walter J Koch; Walter Koch Journal: Circ Res Date: 2012-05-17 Impact factor: 17.367
Authors: Maryam Ahmadian; Jae Myoung Suh; Nasun Hah; Christopher Liddle; Annette R Atkins; Michael Downes; Ronald M Evans Journal: Nat Med Date: 2013-05-07 Impact factor: 53.440