Fractalkine in human inflammatory cardiomyopathy

Background Cardiac inflammation is important for the prognosis of patients with inflammatory cardiomyopathy (CMi), but the mechanisms leading to it are not fully elucidated. Objective To study the role of fractalkine (CX3CL1) in chemotactic and adhesive properties of peripheral blood mononuclear cells (PBMCs) in patients with CMi. Methods and results Patients with enterovirus (EV)-positive CMi, patients with virus-negative CMi, patients with parvovirus B19 (B19) genomes with low intramyocardial inflammation and patients without cardiac inflammation and viral infection in the endomyocardial biopsy (EMB) were enrolled (n=10/group). The expression of CX3CL1 and monocyte chemoattractant protein (MCP-1) in EMBs was significantly increased in EV-positive and virus-negative patients with CMi in contrast to controls and B19-positive patients (EV+ vs controls: CX3CL1-area fraction (AF) % 0.078 +/- 0.012 vs 0.009 +/- 0.003 p < 0.05; MCP-1-AF % 0.093 +/- 0.023 vs 0.011 +/- 0.009). The receptor (CX3CR1)-mediated chemotaxis was increased twofold in PBMCs in comparison with those of controls. The MCP-1 secretion was 3.1-fold higher in PBMCs from EV-positive patients compared with controls, and this elevation was further increased by CX3CL1 in EV-positive patients. No significant CX3CL1-mediated MCP-1 increase was seen in PBMCs from healthy controls. Moreover, spontaneously beating neonatal rat cardiomyocytes exposed to CX3CL1 exhibited an attenuated positive chronotropic response to beta-adrenergic stimulation with isoproterenol. Conclusion The cardiac and plasma CX3CL1/CX3CR1 system is upregulated in CMi and this affects the functional potential of PBMCs. Moreover, a direct cardiodepressive effect of CX3CL1 in cardiac tissue was demonstrated since neonatal cardiomyocytes exhibited an attenuated positive chronotropic response to beta-adrenergic stimulation.