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

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

Adipokine Imbalance in the Pericardial Cavity of Cardiac and Vascular Disease Patients

<div><p>Aim</p><p>Obesity and especially hypertrophy of epicardial adipose tissue accelerate coronary atherogenesis. We aimed at comparing levels of inflammatory and atherogenic hormones from adipose tissue in the pericardial fluid and circulation of cardiovascular disease patients.</p><p>Methods and Results</p><p>Venous plasma (P) and pericardial fluid (PF) were obtained from elective cardiothoracic surgery patients (n = 37). Concentrations of leptin, adipocyte fatty acid-binding protein (A-FABP) and adiponectin (APN) were determined by enzyme-linked immunosorbent assays (ELISA). The median concentration of leptin in PF (4.3 (interquartile range: 2.8–9.1) μg/L) was comparable to that in P (5.9 (2.2–11) μg/L) and these were significantly correlated to most of the same patient characteristics. The concentration of A-FABP was markedly higher (73 (28–124) versus 8.4 (5.2–14) μg/L) and that of APN was markedly lower (2.8 (1.7–4.2) versus 13 (7.2–19) mg/L) in PF compared to P. APN in PF was unlike in P not significantly related to age, body mass index, plasma triglycerides or coronary artery disease. PF levels of APN, but not A-FABP, were related to the size of paracardial adipocytes. PF levels of APN and A-FABP were not related to the immunoreactivity of paracardial adipocytes for these proteins.</p><p>Conclusion</p><p>In cardiac and vascular disease patients, PF is enriched in A-FABP and poor in APN. This adipokine microenvironment is more likely determined by the heart than by the circulation or paracardial adipose tissue.</p></div

Venous plasma and pericardial fluid concentrations of leptin (left), adipocyte fatty acid-binding protein (A-FABP, middle) and adiponectin (right) in cardiac and vascular disease patients (n = 36–37).

<p>Top, box plots illustrating median values, interquartile range and range of concentrations compared by Wilcoxon matched-pairs signed rank test. Bottom, double logarithmic plots by Pearson’s correlation illustrating the relationship between pericardial fluid concentrations and circulating levels of the adipokines.</p

Representative Western blot images of APN multimers in pericardial fluid (left) and venous plasma (right) of cardiac and vascular disease patients.

<p>The Western blots illustrate the composition of oligomeric complexes of APN in pericardial fluid and plasma samples from the same 7 individual patients, indicated by numbers 4–10. The contribution of high molecular APN species (> 200 kDa) to the total concentration of APN was calculated as a percentage as described in the methods section.</p

Patient properties, plasma characteristics and prescribed medications.

<p>Patient properties, plasma characteristics and prescribed medications.</p