Metabolic changes in diastolic heart failure: a proteomic approach

Currently, diastolic heart failure (DHF) is recognized an important cause of cardiovascular mortality and morbidity reaching approximately 50% of HF cases. The growing incidence of cardiovascular risk factors, such as obesity and overweight are associated with a worse prognosis in patients with cardiovascular disease, prompting the onset of diastolic dysfunction. In fact, currently the adipose tissue is considered an important modulator of cardiac function. Adipokines, pro-inflammatory cytokines and other important substances are released by this tissue and seem to play an important role in the induction of the cardiac dysfunction. Thus, considering the high prevalence of obesity in patients with diastolic dysfunction and lack of information about this relation, the aim of this work is to characterize the profile of substances released by adipose tissue under conditions of DHF, using a proteomic approach. The visceral (VAT) and epicardial (EAT) adipose tissue from obese animals with diastolic HF (n=3, obese ZSF1) with their respective lean controls without diastolic HF (n=3, lean ZSF1) were analysed. Firstly, the optimization of methodology for analysis of tissues proteome was performed, testing three different extraction protocols. The selection of protocol was made considering the larger number of extracted proteins, since it there were no significant differences in performed evaluations. After execution of the extracted protocol elected, it was performed the separation of proteins and peptides by one-dimension gel electrophoresis and high-performance liquid chromatography and tryptic digestion used to further mass spectrometry identification. In VAT, the results showed in obesity a decrease of catalase protein and increase of superoxide dismutase, peroxiredoxin-1 and A1 and A2-annexin proteins leading to believe that there are inflammation, oxidative stress and, at the same time, a metabolism protection in order to prevent the increase of reactive oxygen species and progression of inflammation. In addition, it was also was evidenced a decrease of the aldehyde dehydrogenase, mitochondrial suggesting greater susceptibility to oxidative stress. In EAT of the obese ZSF1, the results presents a decrease of 3-ketoacyl-CoA thiolase protein enzyme as a compensatory mechanism in order to inhibit fatty acid oxidation and an increase of lumican and collagen-alpha-1(I) proteins suggesting a link between inflammation caused by obesity and increases of adipose tissue extracellular matrix. Curiously, both tissues demonstrated the increase of cardiac contractile proteins in obese adipose tissue, which are consistent with several reported myofilamentary changes in DHF. Finally, it was analysed differences between the VAT and EAT, which suggest that both tissues present a different proteome. This work is a general approach to the protein composition of the epicardial and visceral adipose tissue of the animal model ZSF1, providing importants differences in adipose tissue proteome between obese animals with DHF and respective controls and helping the future development researches more focused on the functional role of proteins changes in DHF.