Background: Monocytes are implicated in the pathogenesis of atheroscleroticdisease from initiation of atherosclerotic plaque through to plaque instability andrupture. Little is known of the numerical and functional activity of the 3 monocytessubpopulations in the acute and healing phase post ST elevation myocardial infarctionin humans.
Method: 96 patients (aged 64±14; 65% male) were recruited within first 24hourspost percutaneous revascularization for STEMI. Peripheral blood monocyte subsetswere enumerated and characterised using flow cytometry. Monocyte subsetswere defined as CD14++CD16-CCR2+ (Mon1), CD14++CD16+CCR+ (Mon2)and CD14+CD16++CCR2- (Mon3). Functional assessment of monocyte subsetswas assessed by measurement of their phagocytic activity and activation of nuclearfactor Kappa B (NFkB). Median fluorescent intensity (MFI) of intracellularkappa-B kinase beta (IKKβ) was quantified as an index of NFkB pathway activation.Phagocytosis is measured using novel pHrodo E. Coli BioParticles phagocytosiskit. Monocytes characteristics were measused within 24 hours post STEMI,and at 10-14 days (i.e. initiation of healing phase). Transthoracic echocardiographywas performed in the first week.
Results: Monocyte counts were significantly higher at day 1 compared to days10-14. There were no statistical differences in IKKβ levels (p>0.05). The phagocyticactivity of Mon1 and Mon2 increased during the remodeling phase (Table1).Table 1. Monocyte numbers & activity day 1 vs day 14Monocytes [Mean (standard deviation) Day 1 Day 14 P-valueor median (interquartile range)] (T-test or Wilcoxon test)Mon1 (cells/μl) 584 (200); 391 (123); 0.02Mon2 (cells/μl) 96 (59-173) 64 (27-87) <0.001Mon3 (cells/μl) 64 (44-90) 49 (38-71) 0.02Phagocytosis Mon1 (MFI) 104 (28) 115 (28) 0.03Phagocytosis Mon2 (MFI) 84 (35) 109 (32) <0.001Phagocytosis Mon3 (MFI) 29 (10) 30 (15) 0.36High counts of Mon2 and Mon3 at admission were predictive of a lower ejectionfraction (EF) on linear regression analysis (β=-0.28, p=0.02 and β=-0.32, p=0.01)respectively.
Conclusion: Monocyte counts are increased in STEMI patients in the first 24hours post infarction, compared to levels at days 10-14. All monocyte subpopulationsremained functionally at the same level of activity in the acute and healingphases, as detected by IKKβ. The phagocytic activity of the inflammatory monocytessignificantly increased at day 10-14, suggesting a role in debris removaland ventricular remodeling post STEMI. Low EF was predicted by high monocytecounts. This data propose...