The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes

Idźkowska, Ewelina; Eljaszewicz, Andrzej; Mikłasz, Paula; Musiał, Włodzimierz J.; Tycińska, Agnieszka; Moniuszko, Marcin

doi:10.1111/sji.12314

Cited by 93 publications

(77 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In humans, the intermediate CD14 + CD16 + monocytes represent the inflammatory subset and have been implicated in the pathogenesis of various inflammatory diseases including atherosclerosis4243. We asked whether the mechanistic observation in mice may also be reflected in human monocytes.…”

Section: Resultsmentioning

confidence: 99%

The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis

et al. 2016

View full text Add to dashboard Cite

Sustained low-grade inflammation mediated by non-resolving inflammatory monocytes has long been suspected in the pathogenesis of atherosclerosis; however, the molecular mechanisms responsible for the sustainment of non-resolving inflammatory monocytes during atherosclerosis are poorly understood. Here we observe that subclinical endotoxemia, often seen in humans with chronic inflammation, aggravates murine atherosclerosis through programming monocytes into a non-resolving inflammatory state with elevated Ly6C, CCR5, MCP-1 and reduced SR-B1. The sustainment of inflammatory monocytes is due to the disruption of homeostatic tolerance through the elevation of miR-24 and reduction of the key negative-feedback regulator IRAK-M. miR-24 reduces the levels of Smad4 required for the expression of IRAK-M and also downregulates key lipid-processing molecule SR-B1. IRAK-M deficiency in turn leads to elevated miR-24 levels, sustains disruption of monocyte homeostasis and aggravates atherosclerosis. Our data define an integrated feedback circuit in monocytes and its disruption may lead to non-resolving low-grade inflammation conducive to atherosclerosis.

show abstract

Section: Resultsmentioning

confidence: 99%

The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Similarly, the relative proportion of specific monocyte subsets has been linked to adverse outcomes in patients suffering from cardiovascular disease (3, 4, 11, 12). Monocyte subsets characterized by their variable expression of lipopolysaccharide receptor CD14 and Fcγ-III receptor CD16 in peripheral blood have been traditionally divided into classical (CD14++CD16−, M1), intermediate (CD14++CD16+), and non-classical (CD14+CD16+, M2) monocytes (13, 14).…”

Section: Introductionmentioning

confidence: 99%

“…Monocyte subsets characterized by their variable expression of lipopolysaccharide receptor CD14 and Fcγ-III receptor CD16 in peripheral blood have been traditionally divided into classical (CD14++CD16−, M1), intermediate (CD14++CD16+), and non-classical (CD14+CD16+, M2) monocytes (13, 14). Several studies have suggested that increased expression of CD16 either with a greater proportion in intermediate or non-classical monocytes can be used to predict adverse events in patients with heart disease (3, 13). Moreover, in a large study of 951 patients undergoing elective coronary angiography, Rogacev and colleagues were able to demonstrate how elevated values of intermediate monocytes could independently be used to predict long-term adverse cardiovascular outcomes in these patients (4).…”

Section: Introductionmentioning

confidence: 99%

Changes in Circulating Monocyte Subsets (CD16 Expression) and Neutrophil-to-Lymphocyte Ratio Observed in Patients Undergoing Cardiac Surgery

Gawdat

Legere

Wong

et al. 2017

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundThe characteristics of circulating inflammatory cells (leukocytes) in patients undergoing heart surgery remains poorly understood. Recently, neutrophil-to-lymphocyte ratio (NLR) and specific monocyte subsets (based on CD14/CD16 expression) have been suggested as markers of inflammation and predictors of outcomes. The present study aims to characterize the influence cardiac surgery with cardiopulmonary bypass has on specific circulating leukocytes.MethodsAll enrolled patients had blood samples taken pre- (0 days), early post- (5 days), and late post- (90 days) surgery. Complete blood counts were performed and whole leukocyte isolations were obtained from blood samples and analyzed with flow cytometry. Fluorophore-linked antibodies (CD45, CD11b, CD14, and CD16) were added to the blood cell isolations and later assessed by flow cytometry.ResultsSeventeen patients were enrolled and samples obtained at 0, 5, and 90 days. We demonstrated a significant increase in NLR (2.2-fold; p = 0.0028) and CD16 mean fluorescence index (MFI-measure fluorescence intensity shift of CD16 in a gated cell population) early at day 5 (2.0-fold; p = 0.0051). Both NLR and CD16 MFI levels generally returned to normal by day 90. There was a significant positive correlation between NLR and CD16 MFI (r2 = 0.29; p = 0.0064). Adverse cardiovascular event (AE) was defined as prolonged length of hospitalization or readmission to hospital for cardiac reasons after discharge was seen in 59% of patients (no deaths occurred). In an unadjusted analysis of AE, we identified NLR as a likely predictor of AE, which meant that patients developing AE had a significantly higher baseline NLR (p = 0.0065), something that was not observed with CD16 MFI (p = 0.2541).ConclusionCardiac surgery is associated with a significant increase in NLR and CD16 MFI (non-classical monocytes) early after surgery corresponding to the early inflammatory phase after surgery. Furthermore, we have, for the first time, identified a significant correlation between NLR and CD16 MFI. While the mechanism for this relationship remains unclear, our findings support the use of a simple test of NLR as a biomarker of inflammation for predicting outcomes in cardiac surgery patients.

show abstract

“…Classical monocytes (CD14++, CD16-) are highly phagocytic cells and produce ROS, whereas the non-classical monocytes (CD14+, CD16++) patrol the endothelium and are involved in autoimmune diseases. The role of intermediate monocytes (CD14++, CD16+) is still controversial as they are associated with inflammatory diseases and release of IL-1β and TNF-α, but also with production of IL-10 [54,55]. Platelets preferentially bind to CD16+ monocytes and may also induce a phenotypical switch of classical monocytes towards CD16+ subsets [22].…”

Section: Monocyte Differentiationmentioning

confidence: 99%

Platelet Interaction with Innate Immune Cells

Kral¹,

Schrottmaier²,

Salzmann³

et al. 2016

Transfus Med Hemother

201

174

View full text Add to dashboard Cite

Platelets are key players in haemostasis and prevent excessive bleeding upon injury. In response to vessel damage, platelets adhere and get activated at sites of injury, leading to recruitment of further platelets and thrombus formation. As injury represents a risk for infection, platelets recruit and activate leukocytes via direct cell-cell contacts and indirectly via cytokines and platelet-derived microvesicles. Activated platelets directly interact with leukocytes via P-selectin (CD62P) interaction with P-selectin glycoprotein ligand 1 (PSGL-1). This initial binding is enhanced by interaction of various other receptors, depending on the leukocyte subtype, leading to mutual activation and local cytokine release (reviewed in [1]), which modulates immune responses.Upon activation platelets release a variety of α-granule-derived cytokines, chemokines and growth factors [2]. The mechanism of packaging inflammatory cargo into α-granules, however, is incompletely understood [3]. Cytokines can be packaged into granules during megakaryopoiesis [4] either via biosynthesis in the megakaryocyte (e.g. platelet factor 4/CXCL4) or via endocytosis from the microenvironment (e.g. albumin) in the bone marrow [3]. Despite lacking a nucleus, platelets can splice and de novo synthesise proteins from megakaryocyte-derived (pre)mRNA as shown for 6]. Via their open canalicular system platelets also take up factors from the circulation. Further platelets can fuse with microvesicles, which leads to intercellular exchanges of chemotactic receptors such as C-C chemokine receptor type 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) [7,8]. Platelet cytokine levels have been demonstrated to be elevated in cancer patients [9,10], indicating either an active uptake of these factors by platelets or disease-related changes in megakaryopoiesis. This suggests that underlying pathologies might influence not only platelet reactivity but also their potential to modulate immune responses. KeywordsPlatelets · Platelet-leukocyte aggregates · P-selectin · Inflammation · Infection · Cardiovascular disease SummaryBeyond their traditional role in haemostasis and thrombosis, platelets are increasingly recognised as immune modulatory cells. Activated platelets and platelet-derived microparticles can bind to leukocytes, which stimulates mutual activation and results in rapid, local release of platelet-derived cytokines. Thereby platelets modulate leukocyte effector functions and contribute to inflammatory and immune responses to injury or infection. Platelets enhance leukocyte extravasation, differentiation and cytokine release. Platelet-neutrophil interactions boost oxidative burst, neutrophil extracellular trap formation and phagocytosis and play an important role in host defence. Platelet interactions with monocytes propagate their differentiation into macrophages, modulate cytokine release and attenuate macrophage functions. Depending on the underlying pathology, platelets can enhance or diminish leukocyte cytokine production, indicating that pla...

show abstract

The Role of Different Monocyte Subsets in the Pathogenesis of Atherosclerosis and Acute Coronary Syndromes

Cited by 93 publications

References 125 publications

The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis

The persistence of low-grade inflammatory monocytes contributes to aggravated atherosclerosis

Changes in Circulating Monocyte Subsets (CD16 Expression) and Neutrophil-to-Lymphocyte Ratio Observed in Patients Undergoing Cardiac Surgery

Platelet Interaction with Innate Immune Cells

Contact Info

Product

Resources

About