ABSTRACT
Pericardial fluid, as a biochemical indicator of heart status, directly indicates pathological alteration to the heart. The accumulation of pericardial fluid can be attributed to an underlying systemic or local inflammatory process. However, the pericardial fluid expression of cellular surface markers, as well as several cytokines in chronic heart failure (CHF), remain unclear. In order to evaluate these issues further the pericardial fluid expression of several cytokines and the surface expression of activity markers between CHF patients and non-heart failure (NHF) patients were analyzed. The pericardial fluid expression of cytokines was measured by immunofluorescence and biomarker of plasma N-terminal propeptide of B-type natriuretic peptide (NT-proBNP), while pericardial fluid levels of soluble glycoprotein 130 (sgp130) were analyzed by ELISA in 50 CHF and 24 NHF patients. In addition, the surface expression of activation markers for T-cells was measured by immunohistochemistry. Patients with CHF demonstrated increased levels of plasma NT-proBNP and pericardial fluid sgp130. Surface expression of cellular activation markers CD25 and Foxp3 in the pericardial fluid was increased in patients with CHF. Moreover, the pro- and anti-inflammatory cytokines interferon (IFN)-γ, interleukin (IL)-6 and IL-10 in patients with CHF also demonstrated an increased expression within its pericardial fluid. In addition, there was infiltration of inflammatory cells and enhanced expression of inflammatory cytokines in the pericardial fluid of patients with CHF, which may reflect T cell activation, suggesting that systemic inflammation is important in the progression of CHF. This evidence could indicate a possible novel target for future therapeutics and prevention of CHF.
ABSTRACT
BACKGROUND: Despite their importance, the current clinical biomarkers of chronic heart failure have limitations. In this study, soluble glycoprotein 130 (sgp130), heat shock protein 27 (hsp27), dipeptidyl peptidase IV (dpp4) and cathepsin S (CTSS) were tested for their potential as novel biomarkers for diagnosing chronic heart failure (CHF) with preserved ejection fraction. METHODS: We compared the circulating levels of sgp130, hsp27, dpp4, and cathepsin S in patients with CHF with preserved ejection fraction (n=50) and in controls (n=50), determined how well these candidate biomarkers distinguish patients with CHF from controls, and assessed whether these candidates are superior to N-terminal pro brain natriuretic peptide (NT-pro-BNP) as diagnostic tools. RESULTS: After adjusting for clinical covariates, patients with CHF showed significantly higher mean concentrations of sgp130 (317.38pg/ml vs. 215.90 pg/ml), hsp27 (2601.02 pg/ml vs. 923.61 pg/ml) and NT-pro-BNP (982.35 pg/ml vs. 331.99 pg/ml), but not dpp4 (6930.9 4pg/ml vs. 7081.37 pg/ml) or CTSS (1050.46 pg/ml vs. 984.96 pg/ml), than did controls. In the receiver operating characteristic curve analysis, hsp27 showed the most notable difference between CHF patients and controls, with the largest area under the curve (AUC) (0.920); the AUC values for sgp130 and NT-pro-BNP were 0.877 and 0.882, respectively. CONCLUSIONS: Soluble glycoprotein 130 and hsp27 are novel candidate biomarkers for diagnosing CHF with preserved ejection fraction and thus warrant further investigation; neither dpp4 nor CTSS showed promise as biomarkers of CHF.
