Abstract
Background: Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking.Methods: In this study, tandem mass tag (TMT) quantitative proteomics was used to identify disease-related proteins and construct disease-related networks. Furthermore, functional enrichment analysis of overlapping network modules was used to determine the functional similarities between HFpEF and HTN. Molecular docking and module analyses were combined to identify therapeutic targets for HFpEF and HTN.Results: Seven common differentially expressed proteins (co-DEPs) and eight overlapping modules were identified in HFpEF and HTN. The common biological processes between HFpEF and HTN were mainly related to energy metabolism. Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were all closely associated with HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate were best matched with the co-DEPs by molecular docking analyses.Conclusion: Myocardial contraction, energy metabolism, apoptosis, oxidative stress, immune response, and cardiac hypertrophy were the main functional connections between HFpEF and HTN. Epinephrine, sulfadimethoxine, chloroform, and prednisolone acetate could potentially be effective for the treatment of HTN and HFpEF.
Highlights
Heart failure with preserved ejection fraction (HFpEF), which is a complex syndrome characterized by a normal left ventricular ejection fraction and abnormal diastolic function, accounts for more than 50% of heart failure (HF) patients (Pieske et al, 2019)
The results showed that cardiac hypertrophy, which is associated with diastolic function, was significantly associated with HFpEF and HTN (Schmieder, 1990)
Seven co-differentially expressed proteins (DEPs) were observed between the HFpEF-DEPs and HTN-DEPs, including Hp, Tf, coenzyme Q9 (COQ9), Acat1, translocase of inner mitochondrial membrane 44 (Timm44), ATP-binding cassette sub-family B member 6 (Abcb6), and prion protein (Prnp)
Summary
Heart failure with preserved ejection fraction (HFpEF), which is a complex syndrome characterized by a normal left ventricular ejection fraction and abnormal diastolic function, accounts for more than 50% of heart failure (HF) patients (Pieske et al, 2019). Compared with heart failure with reduced ejection fraction (HFrEF), HFpEF is heterogeneous, and drugs effective against HFrEF are not suitable for HFpEF (Graziani et al, 2018). Exploring the underlying biological functions involved in the different types of HFpEF will help develop personalized therapies and precision medicines for HFpEF (Borlaug, 2020; Ge, 2020). Exploring the potential biological relationships between heart failure with preserved ejection fraction (HFpEF) and concomitant diseases has been the focus of many studies for the establishment of personalized therapies. Hypertension (HTN) is the most common concomitant disease in HFpEF patients, but the functional connections between HFpEF and HTN are still not fully understood and effective treatment strategies are still lacking
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