Abstract
Background
Heart failure is currently a worldwide systemic disease with high morbidity and mortality and is very common. At present, many studies have shown that heart failure is associated with obesity, hypertension and diabetes, but it is still unable to prevent the disease from progressing. Here, we elucidate the molecular mechanisms of doxorubicin–induced harmful effects on rat cardiac metabolism and function from a new perspective, using metabonomics and Proteomics analysis data.
Methods
The aim of this study was to use metabonomic and proteomic techniques to systematically elucidate the molecular mechanisms of doxorubicin (DOX)–induced heart failure (HF) in rat. In this study, we aimed to systematically elucidate the molecular action of Dox on rats heart and the reasons for DOX–induced the HF mechanism through the metabonomics tandem mass tag (TMT)–based quantitative proteomics approach. Rats were gavaged with DOX (3 mg/kg) for 6 weeks and the plasma metabonomics, cardiac tissue proteomics, histopathology and related proteins expression levels.
Results
A total of 278 proteins and 21 metabolites were significantly altered in rats following DOX treatments. The responsive proteins and metabolites were predominantly involved in Fatty acid metabolism, Glycolysis, glycerophospholipid metabolism, TCA cycle, Glutathione metabolism, Myocardial contraction.
Conclusions
The present study indicates the PTP1B inhibits the expression of HIF-1α by inhibiting the phosphorylation of IRS, leading to disorders of fatty acid metabolism and glycolysis, which together with the decrease of Nrf2, SOD, Cytc and AK4 proteins lead to oxidative stress, suggesting the PTP1B may serve as a potential target in the treatment of heart failure.
Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate
