Proteomic variations in circulating blood of heart failure patients according to iron status
M Tajes, J Francesch, R Ramos-Polo, M D M Ras-Jimenez, S Jovells-Vaque, A E Cosa, N Jose-Bazan, H Morillas, S Jimenez-Marrero, S Yun, P Moliner, C Diez-Lopez, J Gonzalez-Costello, C Enjuanes, J Comin-ColetAbstract
Background
Heart failure (HF) is a highly prevalent clinical syndrome that imposes a substantial burden on patients and healthcare systems. Iron deficiency (ID) is frequently observed in individuals with HF and is consistently associated with adverse clinical outcomes. Intravenous iron supplementation has emerged as an effective therapeutic intervention, as correction of ID has been shown to improve symptoms, reduce hospitalization rates, and enhance health-related quality of life. Nevertheless, the mechanistic role of iron in HF pathophysiology remains incompletely understood. Emerging evidence indicates that ID may exert a direct influence on molecular and cellular processes implicated in the initiation and progression of HF.
The proteome, defined as the complete set of proteins expressed by a genome, is dynamic and varies according to physiological and pathological states. Comprehensive proteomic profiling offers a powerful approach for identifying novel biomarkers of heart failure (HF), which may provide insights into underlying pathophysiological mechanisms and facilitate the discovery of new therapeutic targets.
Objective
This study aims to determine whether the presence of ID in HF patients, and its correction through intravenous iron therapy, is associated with a distinct plasma proteomic profile. Such differences may reflect alterations in mechanistic pathways influenced by ID and their potential relationship with cardiac function and functional capacity in this population.
Methods
Plasma proteomic profiles were analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS) with a 60-minute gradient on an Orbitrap Eclipse mass spectrometer, employing a data-independent acquisition (DIA) approach. The analysis included 60 patients with HF: 30 without ID and 30 with ID, assessed both before and after intravenous iron therapy.
Results and conclusions
HF patients demonstrate specific plasma protein signatures associated with ID status, which affect different pathways. The identification of these biomarkers represents a significant step toward developing strategies to mitigate adverse outcomes and enhance patient well-being.