Proteomic profiling of epicardial fat in heart failure with preserved versus reduced and mildly reduced ejection fraction

Abstract

In order to explore the proteomic signatures of epicardial adipose tissue (EAT) related to the mechanism of heart failure with reduced and mildly reduced ejection fraction (HFrEF/HFmrEF) and heart failure (HF) with preserved ejection fraction (HFpEF), a comprehensive proteomic analysis of EAT was made in HFrEF/HFmrEF (n = 5) and HFpEF (n = 5) patients with liquid chromatography–tandem mass spectrometry experiments. The selected differential proteins were verified between HFrEF/HFmrEF (n = 20) and HFpEF (n = 40) by ELISA (enzyme‐linked immunosorbent assay). A total of 599 EAT proteins were significantly different in expression between HFrEF/HFmrEF and HFpEF. Among the 599 proteins, 58 proteins increased in HFrEF/HFmrEF compared to HFpEF, whereas 541 proteins decreased in HFrEF/HFmrEF. Of these proteins, TGM2 in EAT was down‐regulated in HFrEF/HFmrEF patients and was confirmed to decrease in circulating plasma of the HFrEF/HFmrEF group (p = 0.019). Multivariate logistic regression analysis confirmed plasma TGM2 could be an independent predictor of HFrEF/HFmrEF (p = 0.033). Receiver operating curve analysis indicated that the combination of TGM2 and Gensini score improved the diagnostic value of HFrEF/HFmrEF (p = 0.002). In summary, for the first time, we described the proteome in EAT in both HFpEF and HFrEF/HFmrEF and identified a comprehensive dimension of potential targets for the mechanism behind the EF spectrum. Exploring the role of EAT may offer potential targets for preventive intervention of HF.

Microvascular rarefaction caused by the NOTCH signaling pathway is a key cause of TKI-apatinib-induced hypertension and cardiac damage

“…Left atrial enlargement and dysfunction, including reduced left atrial systolic reserve, can eventually lead to the development of HFpEF (Nagai et al, 2023;Li et al, 2024). Secondly, in patients with chronic systemic inflammation such as hyperemia, systemic secreted inflammatory cytokines can cause the accumulation and inflammatory response of epicardial adipose tissue, which can promote the migration and transformation of mesenchymal stem cells and local secretion of inflammatory cytokines, leading to deep myocardial cell inflammation, increased myocardial stiffness, deep myocardial fibrosis, and finally HFpEF (Obokata et al, 2017;Gevaert et al, 2022;Gao et al, 2023;Rossi et al, 2023). In addition, microcirculation disorders also play an important role in the occurrence and development of HFpEF (Camici et al, 2020).…”

Omics Insights into Epicardial Adipose Tissue: Unravelling Its Molecular Landscape

“…There is insufficient evidence to suggest this protein is secreted by EAT and then released into the circulation, but TGM2 is decreased in EAT and also in the plasma of patients with HFrEF, suggesting a poorer prognosis for HFrEF. TGM2 is a calcium-dependent acyltransferase involved in the progression of heart failure with an important role in stiffening the extracellular matrix and contractility of the myocardium [99].…”