Plasma fibroblast activation protein is decreased in acute heart failure despite cardiac tissue upregulation
Authors:
Marta Delgado-Arija, Patricia Genovés, Lorena Pérez-Carrillo, Irene González-Torrent, Isaac Giménez-Escamilla, Luis Martínez-Dolz, Manuel Portolés, Estefanía Tarazón, Esther Roselló-Lletí
Cardiac fibroblast activation protein (FAP) has an emerging role in heart failure (HF). A paradoxical reduction in its levels in pathological conditions associated with acute processes has been observed. We aimed to identify FAP cardiac tissue expression and its relationship with the main cardiac fibrosis-related signaling pathways, and to compare plasma FAP levels in acute and chronic HF patients.
Methods
Transcriptomic changes were assessed via mRNA/ncRNA-seq in left ventricle tissue from HF patients (n = 57) and controls (n = 10). Western blotting and immunohistochemistry were used to explore FAP protein levels and localization in cardiac tissue. ELISA was performed to examine plasma FAP levels in acute HF (n = 48), chronic HF (n = 15) and control samples (n = 7).
Results
FAP overexpression in cardiac tissue is related to the expression of molecules directly involved in cardiac fibrosis, such as POSTN, THBS4, MFAP5, COL1A2 and COL3A1 (P < 0.001), and is directly and inversely related to pro- and antifibrotic microRNAs, respectively. The observed FAP overexpression is not reflected in plasma. Circulating FAP levels were lower in acute HF patients than in controls (P < 0.05), while chronic HF patients did not show significant changes. The clinical variables analyzed, such as functional class or etiology, do not affect plasma FAP concentrations.
Conclusions
We determined that in HF cardiac tissue, FAP is related to the main cardiac fibrosis signaling pathways as well as to pro- and antifibrotic microRNAs. Additionally, an acute phase of HF decreases plasma FAP levels despite the upregulation observed in cardiac tissue and regardless of other clinical conditions.
Plasma fibroblast activation protein is decreased in acute heart failure despite cardiac tissue upregulation
Authors
Marta Delgado-Arija Patricia Genovés Lorena Pérez-Carrillo Irene González-Torrent Isaac Giménez-Escamilla Luis Martínez-Dolz Manuel Portolés Estefanía Tarazón Esther Roselló-Lletí
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