Intermediate and nonclassical monocytes show heterogeneity in patients with different types of acute coronary syndrome (original) (raw)
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Prognostic value of monocyte cell markers early after acute myocardial infarction
Journal of the American College of Cardiology, 2003
S-Myocardial Ischemia and Infarction JACC March 19,2003 vascular (CV) events (n=32 CV in 24 pts; 1.3 CV/pt), including death (n=4 pts), urgent PTCA (n=9 pts) or bypass grafting (n=7 pts), re-AMI (n=5 pts) and recurrent angina >2 CCS (n=7 pts). Our AMI population (n=40 pts) was divided into 2 groups according to the occurence of major CV events at 6 months, CV-@=I6 pts) and CV+ (n=24 pts). Between day l-10 post AMI, the CV+ group registered significant differences concerning the MCM mean values of CD1 1 b (194*35 cells/mm~, CD43 (44.9220 cellsimm3) and CD1 1 b/43 (6.7t2.2) when compared with the CV-group values of CD11 b (157.5+28 cells/mm3; p=O.Oi), CD43 (44.8*17 cells/mm3; p=ns) and CD11 b/43 (4.4i1.9: p=O.Ol). MCM evaluation early after the onset of acute ischsmia reflect the degree of cell inflammation and recruitment associated with plaque instability and myocardial infarction, revealing a clear prognostic value in the long term follow-up of this ischemic coronary pathology.
Scandinavian Journal of Immunology, 2015
The inflammation underlying both atherosclerosis and acute coronary syndromes is strongly related to monocyte-related actions. However, different monocyte subsets can play differential roles in the formation and destabilization of atherosclerotic plaque as well as healing of damaged myocardial tissue. Monocytes are currently being divided into three functionally distinct subsets with different levels of CD14 (cluster of differentiation 14) and CD16 expression. Thus, there are classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Here, we summarize the current knowledge on complex activities of different monocyte subsets in atherosclerosis and acute coronary syndromes. Moreover, we discuss which monocyte subsets can serve either as predictive biomarkers of cardiovascular risk or as potential targets used in atherosclerosis and its complications.
Journal of Proteome Research, 2007
We examined the proteome of circulating mono-cytes of patients with acute coronary syndrome at different times in comparison to that of patients with stable coronary artery disease. On admission, the expression of 18 spot proteins was altered, 10 of which were totally absent. This pattern changed progressively, and at 6 months, there were no differences with the monocyte proteome of stable patients.
Circulation Journal, 2012
Background: Circulating monocytes can be divided into 2 subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the 2 distinct monocyte subsets has not previously been evaluated. We investigated the relationship between the monocyte subsets and the severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). Methods and Results: We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into 3 groups: those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD). In addition, the severity of CAD was evaluated by Gensini score. The 2 monocyte subsets (CD14 + CD16and CD14 + CD16 +) were measured by flow cytometry. Circulating CD14 + CD16 + monocytes were more frequently observed in patients with MVD than in those with SVD or without CAD. The proportion of CD14 + CD16 + monocytes positively correlated with Gensini score (r=0.618, P<0.001). Multivariate logistic regression analysis revealed that the proportion of CD14 + CD16 + monocytes was an independent contributor to MVD (odds ratio: 1.475; 95% confidence interval: 1.273-1.708, P<0.001). Conclusions: A preferential increase in peripheral CD14 + CD16 + monocytes may be closely related to the severity of CAD in patients with SAP.
Circulation Journal, 2010
Background: Recent studies have shown that monocytes in human peripheral blood are heterogeneous. The clinical significance of 2 distinct monocyte subsets as a marker of late in-stent restenosis (ISR) following implantation of bare-metal stents (BMSs) in patients with acute myocardial infarction (AMI) was examined. Methods and Results: Seventy-one consecutive patients with AMI who underwent BMS implantation were enrolled in the study. Peripheral blood was collected 12 days after AMI onset. Two distinct monocyte subsets (CD14 + CD16-CCR2 + and CD14 + CD16 + CX3CR1 +) were measured by flow cytometry. All patients underwent angiography at a scheduled follow up after 9 months. CD14 + CD16 + CX3CR1 + monocyte subset counts were significantly higher in patients with restenosis than in patients without restenosis, whereas neither the total monocytes nor the CD14 + CD16-CCR2 + subset counts differed significantly between the 2 groups of patients. There was also a significant positive correlation between the CD14 + CD16 + CX3CR1 + monocyte counts and angiographic late lumen loss. In multivariate analysis, the CD14 + CD16 + CX3CR1 + monocyte count was an independent predictor for in-stent late lumen loss. Conclusions: CD14 + CD16 + CX3CR1 + monocytes might have a role in ISR following coronary BMS implantation in patients with AMI.
Clinical and Experimental Pharmacology and Physiology, 2010
1. In the present study, we investigated the relationships between relative levels of specific peripheral monocyte subsets and coronary flow velocity reserve (CFVR) during the subacute phase in patients with acute myocardial infarction (AMI). 2. The study was performed on 29 patients with primary anterior AMI who had been successfully treated using primary percutaneous coronary intervention. Two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) were measured by flow cytometry. Transthoracic Doppler echocardiography was used to measure CFVR on Days 4 and 7 after the onset of AMI onset. We defined DeltaCFVR as the difference in CFVR values between Days 4 and 7. The extent of myocardial salvage on Day 7 after AMI was evaluated by cardiovascular magnetic resonance (CMR) imaging as the difference between the area of myocardium at risk and the area of necrotic myocardium. 3. There was a significant negative correlation between DeltaCFVR and peak CD14(+)CD16(-) monocyte counts in AMI patients, whereas no significant association was found between CD14(+)CD16(+) monocyte counts and DeltaCFVR. There was a significant positive correlation between DeltaCFVR and the extent of myocardial salvage. 4. In conclusion, peak levels of CD14(+)CD16(-) monocytes following primary anterior AMI were closely related to the extent of microvascular injury.
Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease
Journal of the American College of Cardiology, 2018
Background: Monocytes and macrophages are central to atherosclerosis, but how they mark progression of human coronary artery disease (CAD) is unclear. We tested whether patients' monocyte subtypes paired with their derived macrophage profiles correlate with extent of CAD. Methods: Peripheral blood was collected from 30 patients undergoing cardiac catheterization, and patients were categorized as having no significant CAD, single vessel disease, or multivessel disease according to the number of affected coronary arteries. Mononuclear cells were measured for monocyte markers CD14 and CD16 by flow cytometry, and separate monocytes were cultured into macrophages over 7 days and measured for polarization markers CD86 and CD206. Results: At baseline, patients with greater CAD burden were older with higher rates of statin use, whereas all other characteristics were similar across the spectrum of coronary disease. Non-classical (CD14 lo CD16 hi) and all CD16 + monocytes were elevated in patients with single vessel and multivessel disease compared to those without significant CAD (8.6% and 10.5% vs. 2.8%, p < 0.05), whereas regulatory M2 macrophages (CD206 +) were decreased in patients with single vessel and multivessel disease (0.34% and 0.34% vs. 1.4%, p < 0.05). An inverse relationship between paired CD16 + monocytes and M2 macrophages marked CAD severity. CAD was also found to be more tightly associated with CD16 + cells than age or traditional cardiovascular risk factors on multiple regression analysis of these patients. Conclusions: CAD extent is correlated directly with CD16 + monocytes and inversely with M2 (CD206 +) macrophages, suggesting circulating monocytes may influence downstream polarization of lesional macrophages. These measures of monocyte and macrophage subtypes hold potential as biomarkers in CAD. .
Suppression of inflammatory signaling in monocytes from patients with coronary artery disease
Journal of Molecular and Cellular Cardiology, 2009
Monocytes and T-cells play an important role in the development of atherosclerotic coronary artery disease (CAD). Transcriptome analysis of circulating mononuclear cells from carefully matched atherosclerotic and control patients will potentially provide insights into the pathophysiology of atherosclerosis and supply biomarkers for diagnostic purposes. From patients undergoing coronary angiography because of anginal symptoms, we carefully matched 18 patients with severe triple-vessel CAD to 13 control patients without angiographic signs of CAD. All patients were on statin and aspirin treatment. Elevated soluble-ICAM levels demonstrated increased vascular inflammation in atherosclerotic patients. RNA from circulating CD4+ T-cells, CD14+ monocytes, lipopolysaccharide-stimulated monocytes, and macrophages was subjected to genomewide expression analysis. In CD14+ monocytes, few inflammatory genes were overexpressed in control patients, while atherosclerotic patients showed overexpression of a group of Krüppel-associated box -containing transcription factors involved in negative regulation of gene expression. These differences disappeared upon LPS-stimulation or differentiation towards macrophages. No consistent changes in T cell transcriptomes were detected. Large inter-individual variability prevented the use of single differentially expressed genes as biomarkers, while monocyte gene expression signature predicted patient status with an accuracy of 84%. In this comprehensive analysis of circulating cell transcriptomes in atherosclerotic CAD, cautious patient matching revealed only small differences in transcriptional activity in different mononuclear cell types. Only an indication of a negative feedback to inflammatory gene expression was detected in atherosclerotic patients. Transcriptome differences of circulating cells possibly play less of a role than hitherto thought in the individual patient's susceptibility to atherosclerotic CAD, when appropriately matched for clinical symptoms and medication taken.