A Novel Activator of C-C Chemokine, FROUNT, is Expressed With C-C Chemokine Receptor 2 and its Ligand in Failing Human Heart

BackgroundA novel activator of C-C chemokines, FROUNT, directly binds C-C chemokine receptor (CCR) 2 and plays a central role in the chemokine system. Activation of the chemokine system appears to be involved in the pathogenesis of congestive heart failure (CHF). The purpose of this study was to determine whether FROUNT is expressed with CCR2 and its ligand (CCL2) in failing human heart.Methods and ResultsWe examined endomyocardial biopsy tissues obtained from 71 patients with CHF (HF group) and 20 subjects without CHF (non-HF group). FROUNT, CCR2, and CCL2 mRNA levels were higher in the HF group than in the non-HF group (P < .001). FROUNT mRNA levels were positively correlated with CCR2 and CCL2 mRNA levels in the HF group. FROUNT and CCL2 signal was seen in the cytoplasm of cardiac myocytes in failing hearts. Levels of FROUNT mRNA were negatively correlated with left ventricular ejection fraction. FROUNT, CCR2, and CCL2 mRNA levels were higher in the severe HF subgroup than in the mild HF subgroup.ConclusionsThe expression of FOUNT-mediated CCL2/CCR2 may have important implications in the pathogenesis of CHF. The CCL2/CCR2 pathway via FROUNT may influence the clinical severity of CHF.