Functional characteristics of monocytes subsets in the acute and healing phases of ST elevation myocardial infarction and their effect on ejection fraction

Angie Ghattas, Gregory Y.H. Lip, Helen R. Griffiths, Eduard S. Shantsila

Research output: Contribution to journalMeeting abstract

Abstract

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...
LanguageEnglish
Article numberP4475
Pages787
Number of pages1
JournalEuropean Heart Journal
Volume33
Issue numberSuppl.1
DOIs
Publication statusPublished - 24 Aug 2012
EventESC Congress 2012 - Munchen, Germany
Duration: 25 Aug 201229 Aug 2012

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Monocytes
ST Elevation Myocardial Infarction
Ventricular Remodeling
Atherosclerotic Plaques
Phagocytosis
Infarction
Linear Models
Flow Cytometry
Phosphotransferases
Regression Analysis
Escherichia coli

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Ghattas, Angie ; Lip, Gregory Y.H. ; Griffiths, Helen R. ; Shantsila, Eduard S. / Functional characteristics of monocytes subsets in the acute and healing phases of ST elevation myocardial infarction and their effect on ejection fraction. In: European Heart Journal. 2012 ; Vol. 33, No. Suppl.1. pp. 787.
@article{2ce3aa64ff14416a92c30ce18209c72f,
title = "Functional characteristics of monocytes subsets in the acute and healing phases of ST elevation myocardial infarction and their effect on ejection fraction",
abstract = "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...",
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Functional characteristics of monocytes subsets in the acute and healing phases of ST elevation myocardial infarction and their effect on ejection fraction. / Ghattas, Angie; Lip, Gregory Y.H.; Griffiths, Helen R.; Shantsila, Eduard S.

In: European Heart Journal, Vol. 33, No. Suppl.1, P4475, 24.08.2012, p. 787.

Research output: Contribution to journalMeeting abstract

TY - JOUR

T1 - Functional characteristics of monocytes subsets in the acute and healing phases of ST elevation myocardial infarction and their effect on ejection fraction

AU - Ghattas, Angie

AU - Lip, Gregory Y.H.

AU - Griffiths, Helen R.

AU - Shantsila, Eduard S.

PY - 2012/8/24

Y1 - 2012/8/24

N2 - 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...

AB - 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...

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U2 - 10.1093/eurheartj/ehs283

DO - 10.1093/eurheartj/ehs283

M3 - Meeting abstract

VL - 33

SP - 787

JO - European Heart Journal

T2 - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - Suppl.1

M1 - P4475

ER -