ABSTRACT
[This corrects the article DOI: 10.1007/s11818-018-0154-8.].
ABSTRACT
Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+) intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c(+) dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.
Subject(s)
Amino Sugars/analysis , Monocytes/classification , Receptor, Macrophage Colony-Stimulating Factor/genetics , Receptors, IgG/analysis , Antigens, CD1/analysis , Dendritic Cells/chemistry , Female , Flow Cytometry , GPI-Linked Proteins/analysis , Gene Expression Profiling , Genes, MHC Class II , Genome-Wide Association Study , Glycoproteins/analysis , HLA-D Antigens/analysis , Humans , Immunomagnetic Separation , Leukoencephalopathies/genetics , Leukoencephalopathies/immunology , Leukoencephalopathies/pathology , Lipopolysaccharide Receptors/analysis , Male , Middle Aged , Monocytes/chemistry , Monocytes/immunology , Point Mutation , Reverse Transcriptase Polymerase Chain Reaction , Sarcoidosis/immunology , Sarcoidosis/pathology , Young AdultABSTRACT
AIMS: Sleep-disordered breathing (SDB) may be a risk factor for expansion of infarct size early after acute myocardial infarction (MI) by exposing the heart to repetitive oxygen desaturations and increased cardiac afterload. The objective of this study was to assess the impact of SDB on myocardial salvage and infarct size within 3 months after acute MI. METHODS AND RESULTS: Patients with acute MI and percutaneous coronary intervention were enrolled in this prospective observational study. All patients underwent cardiovascular magnetic resonance (CMR) to define salvaged myocardium and infarct size within three to five days and at 3 months after acute MI. Patients were stratified according to apnoea-hypopnoea index (AHI) assessed by polysomnography at baseline into those with (AHI ≥ 15/h) and without (AHI < 15/h) SDB. Of the 56 patients included, 29 (52%) had SDB. The area at risk between both groups was similar (40 ± 12% vs. 40 ± 14%, P = 0.925). Patients with SDB had significantly less salvaged myocardium (myocardial salvage index 52% vs. 77%, P < 0.001), smaller reduction in infarct size (0.3% vs. 6.5%, P < 0.001) within 3 months after acute MI, a larger final infarct size (23% vs. 12%, P < 0.001), and a lower final left ventricular ejection fraction (48% vs. 54%, P = 0.023). In a multivariate analysis, including established risk factors for large MI, AHI was independently associated with less myocardial salvage and a larger infarct size 3 months after acute MI. CONCLUSIONS: Sleep-disordered breathing was associated with less myocardial salvage and a smaller reduction in infarct size. These findings suggest a contribution of SDB to impaired healing of MI.
Subject(s)
Myocardial Infarction/pathology , Sleep Apnea Syndromes/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/therapy , Percutaneous Coronary Intervention , Polysomnography , Prospective Studies , Quality of Life , Risk Factors , Salvage Therapy , Sleep Apnea Syndromes/complications , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/pathology , Young AdultABSTRACT
BACKGROUND: Sleep-disordered breathing (SDB) may promote an increase in cardiac workload early after acute myocardial infarction (AMI). We tested the hypothesis that in the early phase after AMI, SDB is associated with increased 24-h arterial BP, heart rate (HR), and, thus, cardiac workload. METHODS: In this prospective study, 55 consecutive patients with AMI and subsequent percutaneous coronary intervention (78% men; mean age, 54 ± 10 y; mean BMI, 28.3 ± 3.6 kg/m²; mean left ventricular ejection fraction [LVEF], 47% ± 8%) underwent polysomnography and 24-h ambulatory BP and heart rate monitoring within 5 days after MI. Cardiac workload was calculated as systolic BP multiplied by HR. The presence of SDB was defined as ≥ 10 apneas and hypopneas per hour of sleep. RESULTS: Fifty-five percent of the patients had SDB, of which 40% was predominantly central in nature. Patients with SDB had higher 24-h HR and systolic and diastolic BP compared with those without SDB (115 vs 108 mm Hg, P = .029; 71 vs 67 mm Hg, P = .034; 69 vs 64 beats/min, P = .050, respectively). Use of antihypertensive medication and ß-receptor blockers was similar in both groups. In a multivariate linear regression analysis, SDB was significantly associated with an increased 24-h cardiac workload (ß-coefficient, 0.364; 95% CI, 0.071-0.657; P = .016), independently of age, sex, BMI, LVEF, and antihypertensive medication. CONCLUSION: Patients with AMI and SDB have significantly increased 24-h BP, HR, and cardiac workload. Treatment of SDB may be a valuable nonpharmacologic approach to lower cardiac workload in these patients.
