Treatment with antibodies to CINC-1 significantly reduced RV neutrophil accumulation (52% reduction) and cardiac troponin I by 90% in rats with experimental pulmonary embolism.
Does inhibition of CINC-1 reduce right ventricular damage in a rat model of pulmonary embolism?
Inhibition of CINC-1 reduces neutrophil-dependent cardiac inflammation and right ventricular damage in a rat model of pulmonary embolism.
Effect estimate: 52% reduction in tissue myeloperoxidase; 90% reduction in cardiac troponin I
Right ventricular (RV) dysfunction is a strong risk factor for poor clinical outcome following pulmonary embolism (PE), the third most prevalent cardiovascular disease. Previous studies in our laboratory demonstrated that RV failure during PE is mediated, in part, by neutrophil-dependant cardiac inflammation. In this study we use DNA microarray analysis of gene expression to demonstrate that PE results in increased expression of the CXC chemokines CINC-1 and CINC-2 between 6 and 18 h after the start of PE in a rat model of PE. Neutrophils accumulate in RV tissue by 18 h, and this inflammation is associated with decreased right heart function. Treatment of rats with Abs to CINC-1 significantly suppressed neutrophil accumulation in RVs during PE (52% reduction in tissue myeloperoxidase) and ameliorated RV failure. In addition, plasma concentration of cardiac troponin I, an established diagnostic marker for cardiac damage, was reduced by 90%. These results suggest that selective anti-inflammatory therapies targeted at neutrophil chemoattractants will reduce cardiac inflammation and reduce RV damage in the setting of PE.
Zagorski et al. (Sat,) conducted a other in Pulmonary embolism. Antibodies to CINC-1 was evaluated on Neutrophil accumulation in right ventricles (tissue myeloperoxidase) and plasma concentration of cardiac troponin I (52% reduction in tissue myeloperoxidase; 90% reduction in cardiac troponin I). Treatment with antibodies to CINC-1 significantly reduced RV neutrophil accumulation (52% reduction) and cardiac troponin I by 90% in rats with experimental pulmonary embolism.