Local enrichment of fatty acid-binding protein 4 in the pericardial cavity of cardiovascular disease patients

PLoS One. 2018 Nov 5;13(11):e0206802. doi: 10.1371/journal.pone.0206802. eCollection 2018.


Background: The pericardial fluid may be representative of the interstitium of the heart. The aim of this study was to discriminate in cardiovascular disease patients between adipocytokines that are produced locally by the heart and those supplied by the circulation.

Methods: Enzyme-linked immunosorbent assays (ELISA) were used to determine levels of N-terminal pro-brain natriuretic peptide (NT-pBNP), fatty acid-binding protein 4 (FABP4), leptin, lipocalin-2, neutrophil elastase, proteinase-3, high sensitivity C-reactive protein (hsCRP) and adiponectin in venous plasma and pericardial fluid harvested during elective cardio-thoracic surgery (n = 132-152).

Results: In pericardial fluid compared to plasma, the levels were significantly smaller (p < 0.001) for leptin, lipocalin-2, neutrophil elastase, proteinase-3, hsCRP and adiponectin. For these biomarkers, the ratio of pericardial fluid-to-plasma level ([PF]/[P], median (interquartile range)) was 0.65 (0.47-1.01), 0.78 (0.56-1.09), 0.23 (0.11-0.60), 0.17 (0.09-0.36), 0.14 (0.08-0.35), and 0.25 (0.15-0.34), respectively. In contrast, pericardial fluid was significantly enriched (p < 0.001) in NT-pBNP ([PF]/[P]: 1.9 (1.06-2.73)) and even more so for FABP4 ([PF]/[P]: 3.90 (1.47-9.77)). Moreover, in pericardial fluid, the adipocytokines interrelated all significantly positive and correlated negative to hsCRP, whereas for NT-pBNP only a significantly positive correlation with adiponectin was found. These interrelations were distinct from those in the plasma, as were the correlations of the pericardial biomarkers with patient characteristics compared to plasma.

Conclusions: In cardiovascular disease patients, the pericardial cavity is a distinct adipocytokine microenvironment in which especially FABP4 is mainly derived from the heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / blood
  • Adipokines / metabolism
  • Adiponectin / blood
  • Adiponectin / metabolism
  • Aged
  • Biomarkers / blood
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / metabolism*
  • Fatty Acid-Binding Proteins / blood
  • Fatty Acid-Binding Proteins / metabolism*
  • Female
  • Humans
  • Leptin / blood
  • Leptin / metabolism
  • Leukocyte Elastase / blood
  • Leukocyte Elastase / metabolism
  • Lipocalin-2 / blood
  • Lipocalin-2 / metabolism
  • Male
  • Middle Aged
  • Myeloblastin / blood
  • Myeloblastin / metabolism
  • Natriuretic Peptide, Brain / blood
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism
  • Pericardium / metabolism*


  • ADIPOQ protein, human
  • Adipokines
  • Adiponectin
  • Biomarkers
  • FABP4 protein, human
  • Fatty Acid-Binding Proteins
  • LCN2 protein, human
  • LEP protein, human
  • Leptin
  • Lipocalin-2
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • C-Reactive Protein
  • ELANE protein, human
  • Leukocyte Elastase
  • Myeloblastin

Grant support

This work was supported by the Odense University Hospital, the University of Southern Denmark, the Danish Council for Independent Research [DFF-4092-00098], the Direktør Kurt Bønnelycke og hustru fru Grethe Bønnelyckes Fond and by grants from the Hong Kong Research Grant Council [17121714, HKU780613M and HKU763312M]; Collaborative Research Funds [C7055-14G] of Hong Kong; and National Basic Research Program of China [973 Program 2015CB553603]. It was conducted within the frame of the elite research centre CIMA - Centre for Individualized Medicine in Arterial Diseases of the Odense University Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.