Abstract 3489: Enhanced Expression of Myeloid-Related Protein Complex (MRP 8/14) Predicts the Severity and Risk of Complications in Acute Myocardial Infarction
Introduction: Myeloid-related protein complex (MRP 8/14), a hetero dimmer of MRP 8 and 14, is expressed in activated human neutrophils and macrophages. Although MRP 8/14 is reported to be involved in the inflammatory process of various diseases, its expression in acute myocardial infarction (AMI) has not been clarified.
Hypothesis: We assessed the hypothesis that serum levels of MRP 8/14 are increased in patients with AMI, and the expression of MRP 8/14 is upregulated in the myocardium of AMI patients.
Methods: Serum MRP 8/14 levels were measured using a sandwich enzyme-linked immunosorbent assay system in 25 consecutive patients [68±2 (SE) years, 17 men and 8 women] with AMI during the acute period continuously, from the onset to the 10th hospital day. Sera from 30 normal volunteers served as controls. All AMI patients underwent successful primary percutaneous coronary intervention within 12 hours after the onset of symptoms. In AMI patients, serum levels of C-reactive protein (CRP) and creatine kinase (CK) were also measured. In addition, we immunohistochemically examined the expression profiles of MRP 8/14 in the autopsied myocardium from 4 patients with AMI.
Results: In AMI patients, serum MRP 8/14 levels on the 1st day were significantly higher than in normal controls [636±86 ng/ml vs. 230±21 ng/ml, p<0.0001] and reached the peak levels on the 4th day (1025±123 ng/ml). The peak MRP 8/14 levels were positively correlated with peak CRP levels (r=0.67, p<0.001) and peak CK levels (r=0.55, p<0.01). In patients with major early phase complications such as cardiac or papillary muscle rupture, and severe heart failure (n=8), the serum MRP 8/14 levels on the 1st hospital day were significantly higher than in those without complications (n=17) (1033±173 ng/ml vs. 555±51 ng/ml, p<0.001). Immunohistochemically, MRP 8/14 was specifically and strongly positive in the cytoplasm of neutrophils and macrophages in the necrotic myocardium from AMI patients.
Conclusions: These findings imply that MRP 8/14, produced by neutrophils and macrophages, plays an important role in the pathogenesis of AMI. The increase in serum MRP 8/14 levels may predict the severity and risk of early phase complications in AMI.