Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction
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ABSTRACT:
SUBMITTER: Askari N
PROVIDER: S-EPMC8592918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In experimental myocardial infarction (MI), a rise in cell counts of circulating monocyte subsets contributes to impaired myocardial healing and to atherosclerotic plaque destabilization. In humans, the prognostic role of monocyte subsets in patients suffering ST-elevation MI (STEMI) is still unclear. In the present study, we aimed to determine the kinetics of the 3 monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+, and nonclassical CD14+CD16++ monocytes), as well as the subset-specific monocyte-platelet aggregates (MPA), in acute STEMI followed by primary percutaneous coronary intervention (PCI), and their relationships with cardiovascular outcomes during a 2-year follow-up.Monocyte subsets and MPA were measured in 100 STEMI patients receiving primary PCI on days 1, 2, 3, 5, and 7 of symptom onset, which were compared with 60 stable coronary heart disease patients and 35 healthy volunteers. From day 1 to day 7, significant increases in the counts of CD14++CD16+ monocytes and CD14++CD16+ MPA were observed, with peak levels on day 2. During a median follow-up of 2.0 years, 28 first cardiovascular events (defined as cardiovascular death, nonfatal ischemic stroke, recurrent MI, need for emergency or repeat revascularization, and rehospitalization for heart failure) were recorded. After adjustment for confounders, CD14++CD16+ monocytosis (day 1 [HR: 3.428; 95% CI: 1.597-7.358; P?=?0.002], day 2 [HR: 4.835; 95% CI: 1.106-21.13; P?=?0.04], day 3 [HR: 2.734; 95% CI: 1.138-6.564; P?=?0.02], and day 7 [HR: 2.647; 95% CI: 1.196-5.861; P?=?0.02]), as well as increased levels of CD14++CD16+ MPA measured on all time points (days 1, 2, 3, 5, and 7), had predictive values for adverse cardiovascular events.In conclusion, our data show the expansion of the CD14++CD16+ monocyte subset during acute phase of STEMI has predictive values for 2-year adverse cardiovascular outcomes in patients treated with primary PCI. Future studies will be warranted to elucidate whether CD14++CD16+ monocytes may become a target cell population for new therapeutic strategies after STEMI.
| S-EPMC4863763 | biostudies-literature
Project description:Neutrophils release their chromatin into the extracellular space upon activation. These web-like structures are called neutrophil extracellular traps (NETs) and have potent prothrombotic and proinflammatory properties. In ST-elevation myocardial infarction (STEMI), NETs correlate with increased infarct size. The interplay of neutrophils and monocytes impacts cardiac remodeling. Monocyte subsets are classified as classical, intermediate and non-classical monocytes. In the present study, in vitro stimulation with NETs led to an increase of intermediate monocytes and reduced expression of CX3CR1 in all subsets. Intermediate monocytes have been associated with poor outcome, while non-classical CX3CR1-positive monocytes could have reparative function after STEMI. We characterized monocyte subsets and NET markers at the culprit lesion site of STEMI patients (n = 91). NET surrogate markers were increased and correlated with larger infarct size and with fewer non-classical monocytes. Intermediate and especially non-classical monocytes were increased at the culprit site compared to the femoral site. Low CX3CR1 expression of monocytes correlated with high NET markers and increased infarct size. In this translational system, causality cannot be proven. However, our data suggest that NETs interfere with monocytic differentiation and receptor expression, presumably promoting a subset shift at the culprit lesion site. Reduced monocyte CX3CR1 expression may compromise myocardial salvage.
| S-EPMC6841683 | biostudies-literature
Project description:BackgroundType 2 myocardial infarction (MI) is defined by a rise and fall of cardiac biomarkers and evidence of ischemia without unstable coronary artery disease (CAD) because of a mismatch in myocardial oxygen supply and demand. Myocardial injury is similar but does not fulfill the clinical criteria for MI. There is uncertainty in terms of the clinical characteristics, management, and outcomes of type 2 MI and myocardial injury in comparison with type 1 MI.Patients and methodsPatients admitted to a Veterans Affairs tertiary care hospital with a rise and fall in cardiac troponin were identified. MI and injury subtypes, presentation, management, and outcomes were determined.ResultsType 1 MI, type 2 MI, and myocardial injury occurred in 137, 146, and 175 patients, respectively. Patients with type 2 MI were older (P=0.02), had lower peak cardiac troponin (P<0.001), and were less likely to receive aspirin and statin at discharge (P<0.001) than type 1 MI survivors. All-cause mortality (median follow-up: 1.8 years) was not different between patient groups (type 1 MI mortality: 29.9%, type 2 MI: 30.8%, myocardial injury: 29.7%; log rank P=0.94). A significant proportion of deaths were attributed to cardiovascular causes in all subgroups (type 1 MI: 34.1%, type 2 MI: 17.8%, myocardial injury: 30.8%).ConclusionPatients with type 2 MI and myocardial injury were less likely to receive medical therapy for CAD than those with type 1 MI. No differences in all-cause mortality among MI subtypes were observed. Additional studies to determine optimal medical therapy and risk stratification strategies for these high-risk populations are warranted.
| S-EPMC5722665 | biostudies-literature
Project description:Monocytes are a heterogeneous population of effector cells with key roles in tissue integrity restoration and maintenance. Here, we explore the association of monocyte subsets and prognosis in patients with ambulatory heart failure (HF). Monocyte subsets were classified as classical (CD14++/CD16-), intermediate (CD14++/CD16+), or non-classical (CD14+/CD16++). Percentage distribution and absolute cell count were assessed in each subset, and multivariable Cox regression analyses were performed with all-cause death, HF-related hospitalization, and the composite end-point of both as dependent variables. 400 patients were consecutively included (72.8% male, age 69.4±12.2 years, 45.5% from ischemic aetiology, left ventricle ejection fraction (LVEF) 41.6% ±14.5, New York Heart Association (NYHA) class II 62.8% and III 30.8%). During a mean follow-up of 2.6±0.9 years, 107 patients died, 99 had a HF-related hospitalization and 160 suffered the composite end-point of all-cause death or HF-related hospitalization. Monocyte subsets assessed in percentages were not independently associated to any of the end-points. When considering number of cells/μL, intermediate subset was independently associated with an increase of all-cause death (HR 1.25 [95% CI 1,02-1.52], p = 0.03), and the composite end-point HR 1.20 [95% CI 1,03-1.40], p = 0.02). The presented findings show that absolute cell count of monocyte subsets was preferred over monocyte percentage for prognosis stratification for outpatients with HF. The intermediate monocyte subset provides information on increased risk of all-cause death and the composite end-point.
| S-EPMC6150659 | biostudies-literature
Project description:ObjectiveCirculating microparticles (cMPs) are phospholipid-rich vesicles released from cells when activated or injured, and contribute to the formation of intracoronary thrombi. Tissue factor (TF, CD142) is the main trigger of fibrin formation and TF-carrying cMPs are considered one of the most procoagulant cMPs. Similar types of atherosclerotic lesions may lead to different types of AMI, although the mechanisms behind are unresolved. Therefore, we aimed to investigate the phenotype of cMPs found in plasma of ACS patients and its relation to AMI severity and thrombotic burden.MethodsIn a cross-sectional study, two hundred patients aged 75±4 years were included in the study 2-8 weeks after suffering an AMI. Annexin V positive (AV+)-cMPs derived from blood and vascular cells were measured by flow cytometry. Plasma procoagulant activity (TF-PCA) was measured through a chromogenic assay.ResultsSTEMI patients (n = 75) showed higher levels of platelet-derived cMPs [CD61+/AV+, CD31+/AV+, CD42b+/AV+ and CD31+/CD42b+/AV+, P = 0.048, 0.038, 0.009 and 0.006, respectively], compared to NSTEMI patients (n = 125). Patients who suffered a heart failure during AMI (n = 17) had increased levels of platelet (CD61+)-and monocyte (CD14+)-derived cMPs carrying TF (CD142+) (P<0.0001 and 0.004, respectively). Additionally, NYHA class III (n = 23) patients showed higher levels of CD142+/AV+, CD14+/AV+ and CD14+/CD142+/AV+ cMPs than those in class I/II (P = 0.001, 0.015 and 0.014, respectively). The levels of these cMPs positively correlated with TF-PCA (r≥0.166, P≤0.027, all).ConclusionsPlatelets and monocytes remain activated in AMI patients treated as per guidelines and release cMPs that discriminate AMI severity. Therefore, TF-MPs, and platelet- and monocyte-MPs may reflect thrombotic burden in AMI patients.
| S-EPMC5313202 | biostudies-literature
Project description:BackgroundThe level of systemic inflammation correlates with the severity of the clinical course of acute myocardial infarction (AMI). It has been shown that circulating cytokines and endothelial dysfunction play an important role in the process of clot formation. The aim of our study was to assess the concentration of various circulating cytokines, endothelial function and blood clotting in AMI patients depending on the blood flow through the infarction-related artery (IRA).MethodsWe included 75 patients with AMI. 58 presented with ST-elevation myocardial infarction (STEMI) and 17 had non-ST-elevation myocardial infarction (non-STEMI). A flow-mediated dilation test (FMD test), thrombodynamics and rotational thromboelastometry as well as assessment of 14 serum cytokines using xMAP technology were performed.FindingsNon-STEMI-patients were characterized by higher levels of MDC, MIP-1β, TNF-α. Moreover, we observed that patients with impaired blood flow through the IRA (TIMI flow 0-1) had higher average and initial clot growth rates, earlier onset of spontaneous clots, C-reactive protein (CRP) and IL-10 compared to patients with preserved blood flow through the IRA (TIMI flow 2-3). Patients with TIMI 2-3 blood flow had higher level of IP-10. IL-10 correlated with CRP and pro-inflammatory cytokines levels, initial clot growth rate and clot lysis time in TIMI 0-1 patients. All these differences were statistically significant.InterpretationWe demonstrated that concentrations of the inflammatory cytokines correlate not only with the form of myocardial infarction (STEMI or non-STEMI), but also with the blood flow through the infarct-related artery. Inflammatory response, functional state of endothelium, and clot formation are closely linked with each other. A combination of these parameters affects the patency of the infarct-related artery.
| S-EPMC8886043 | biostudies-literature
Project description:Collagen is a major determinant of atherosclerotic plaque stability. Thus, identification of differences in enzymes that regulate collagen integrity could be useful for predicting susceptibility to atherothrombosis or for diagnosing plaque rupture. In this study, we sought to determine whether prolidase, the rate-limiting enzyme of collagen turnover, differs in human subjects with acute myocardial infarction (MI) versus those with stable coronary artery disease (CAD).We measured serum prolidase activity in 15 patients with stable CAD and 49 patients with acute MI, of which a subset had clearly defined thrombotic MI (n = 22) or non-thrombotic MI (n = 12). Prolidase activity was compared across study time points (at cardiac catheterization, T0; 6 h after presentation, T6; and at a quiescent follow-up, Tf/u) in acute MI and stable CAD subjects. We performed subgroup analyses to evaluate prolidase activity in subjects presenting with acute thrombotic versus non-thrombotic MI.Although prolidase activity was lower at T0 and T6 versus the quiescent phase in acute MI and stable CAD subjects (p < 0.0001), it was not significantly different between acute MI and stable CAD subjects at any time point (T0, T6, and Tf/u) or between thrombotic and non-thrombotic MI groups. Preliminary data from stratified analyses of a small number of diabetic subjects (n = 8) suggested lower prolidase activity in diabetic acute MI subjects compared with non-diabetic acute MI subjects (p = 0.02).Circulating prolidase is not significantly different between patients with acute MI and stable CAD or between patients with thrombotic and non-thrombotic MI. Further studies are required to determine if diabetes significantly affects prolidase activity and how this might relate to the risk of MI.
| S-EPMC5535509 | biostudies-other
Project description:Although coronary thrombus overlying a disrupted atherosclerotic plaque has long been considered the hallmark and the primary therapeutic target for acute myocardial infarction (MI), multiple other mechanisms are now known to cause or contribute to MI. It is further recognized that an MI is just one of many types of acute myocardial injury. The Fourth Universal Definition of Myocardial Infarction provides a taxonomy for acute myocardial injury, including 5 subtypes of MI and nonischemic myocardial injury. The diagnosis of MI is reserved for patients with myocardial ischemia as the cause of myocardial injury, whether attributable to acute atherothrombosis (type 1 MI) or supply/demand mismatch without acute atherothrombosis (type 2 MI). Myocardial injury in the absence of ischemia is categorized as acute or chronic nonischemic myocardial injury. However, optimal evaluation and treatment strategies for these etiologically distinct diagnoses have yet to be defined. Herein, we review the epidemiology, risk factor associations, and diagnostic tools that may assist in differentiating between nonischemic myocardial injury, type 1 MI, and type 2 MI. We identify limitations, review new research, and propose a framework for the diagnostic and therapeutic approach for patients who have suspected MI or other causes of myocardial injury.
| S-EPMC6855329 | biostudies-literature
Project description:BackgroundAcute myocardial infarction (AMI) is a major contributor of heart failure (HF). Peripheral blood mononuclear cells (PBMCs), mainly monocytes, are the essential initiators of AMI-induced HF. The powerful biomarkers for early identification of AMI patients at risk of HF remain elusive. We aimed to identify monocyte-related critical genes as predictive biomarkers for post-AMI HF.MethodsWe performed weighted gene co-expression network analysis (WGCNA) on transcriptomics of PBMCs from AMI patients who developed HF or did not. Functional enrichment analysis of genes in significant modules was performed via Metascape. Then we obtained the single-cell RNA-sequencing data of recruited monocytes/macrophages from AMI and control mice using the Scanpy and screened 381 differentially expressed genes (DEGs) between the two groups. We validated the expression changes of the 25 genes in cardiac macrophages from AMI mice based on bulk RNA-sequencing data and PBMCs data mentioned above.ResultsIn our study, the results of WGCNA showed that two modules containing 827 hub genes were most significantly associated with post-AMI HF, which mainly participated in cell migration, inflammation, immunity, and apoptosis. There were 25 common genes between DEGs and hub genes, showing close relationship with inflammation and collagen metabolism. CUX1, CTSD and ADD3 exhibited consistent changes in three independent studies. Receiver operating characteristic curve analysis showed that each of the three genes had excellent performance in recognizing post-AMI HF patients.ConclusionOur findings provided a set of three monocyte-related biomarkers for the early prediction of HF development after AMI as well as potential therapeutic targets of post-AMI HF.
| S-EPMC7871627 | biostudies-literature
Project description:BackgroundAcute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI), and is associated with adverse outcomes. The study aimed to identify a miRNA signature for the early diagnosis of post-AMI AKI.MethodsA total of 108 patients admitted to a coronary care unit (CCU) were divided into four subgroups: AMI-AKI-, AMI+AKI-, AMI+AKI+, and AMI-AKI+. Thirty-six miRNA candidates were selected based on an extensive literature review. Real-time quantitative RT-PCR analysis was used to determine the expression levels of these miRNAs in the serum collected on the day of CCU admittance. TargetScan 7.1 and miRDB databases were used for target prediction and Metacore 6.13 was used for pathway analysis.ResultsThrough a stepwise selection based on abundance, hemolytic effect and differential expression between four groups, 9 miRNAs were found to have significantly differential expression levels as potential biomarkers for post-AMI AKI specifically. Noticeably, the expression levels of miR-24, miR-23a and miR-145 were significantly down-regulated in AMI+AKI+ patients compared to those in AMI+AKI- patients. Combination of the three miRNAs as a panel showed the best performance in the early detection of AKI following AMI (AUC = 0.853, sensitivity 95.65%), compared to the analysis of serum neutrophil gelatinase-associated lipocalin (AUC = 0.735, sensitivity 63.16%). Furthermore, bioinformatic analysis indicated that these three miRNAs regulate the transforming growth factor beta signaling pathway and involve in apoptosis and fibrosis in AKI.ConclusionsFor the first time, this study identify a unique circulating miRNA signature (miR-24-3p, miR-23a-3p, miR-145-5p) that can potentially early detect AKI following AMI and may be involved in renal injury and fibrosis in post-AMI AKI pathogenesis.
| S-EPMC6492315 | biostudies-literature