Abstract 1: Human Monocyte Diversity in Cardiovascular Disease Revealed by Mass Cytometry

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Anouk A Hamers ◽  
Graham D Thomas ◽  
Cheryl Kim ◽  
Anh T Nguyen ◽  
Chantel McSkimming ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Suppressor Cells ◽  
Human Monocyte ◽  
Significant Heterogeneity ◽  
Monocyte Subsets ◽  
Mass Cytometry ◽  
Healthy Human ◽  
Healthy Humans ◽  
New Information ◽  
Healthy Donors

Background: Monocytes are critical to the initiation and development of atherosclerosis. To date, 3 distinct human monocyte subsets have been identified based primarily on their expression of the surface markers CD14 and CD16. With the emerging knowledge of myeloid-derived suppressor cells and other myeloid subsets, we hypothesized that monocytes are likely more heterogeneous in composition. Therefore, we set out to use the high dimensionality of mass cytometry to accurately identify and define monocyte subsets in blood of healthy humans and their changes in cardiovascular patients. Methods: Heparinized blood from 12 healthy donors and 15 patients with defined cardiovascular disease (CVD) based on angiography and gensini score was obtained and analyzed by CyTOF mass cytometry. We employed the Phenograph algorithm to cluster and identify all healthy monocyte subsets based on their phenotypes using a 40-marker mass cytometry panel. Results: Phenograph identified a total of 15 monocyte clusters in healthy human blood. By performing hierarchical clustering, we were able to group these clusters into 6 larger meta-clusters and found that most of these meta-clusters fall within the CD14 classical monocyte population, illustrating significant heterogeneity among this monocyte population. Cell numbers of one of these monocyte meta-clusters were significantly increased in blood from patients with CVD. We also identified two subsets of nonclassical monocytes in healthy donors. One of these subsets showed higher expression of the integrin CD61 and tetraspanin CD9, pointing to a possible role for this subset in patrolling and platelet activation. Conclusion: Monocytes are highly diverse with the conventional classical subset showing the most diversity. The numbers and frequencies of some of these monocyte subsets are changed in CVD. Studies to identify their functions in CVD should provide new information for the role of monocytes in CVD.

scholarly journals Immunophenotypic characterization of human monocyte subsets: possible implications for cardiovascular disease pathophysiology

2011 ◽  
Vol 9 (5) ◽  
pp. 1056-1066 ◽  
Author(s):  
E. SHANTSILA ◽  
B. WRIGLEY ◽  
L. TAPP ◽  
S. APOSTOLAKIS ◽  
S. MONTORO-GARCIA ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Human Monocyte ◽  
Monocyte Subsets

scholarly journals Aging and interferon gamma response drive the phenotype of neutrophils in the inflamed joint

2021 ◽  
Author(s):  
Ricardo Grieshaber-Bouyer ◽  
Tarik Exner ◽  
Nicolaj S Hackert ◽  
Felix A Radtke ◽  
Scott A Jelinsky ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Interferon Gamma ◽  
Ex Vivo ◽  
Joint Fluid ◽  
Mass Cytometry ◽  
Healthy Human ◽  
Healthy Donors ◽  
Active Arthritis ◽  
Blood Neutrophils ◽  
Prominent Response

Objectives: Neutrophils are typically the most abundant leukocyte in arthritic synovial fluid. We sought to understand changes that occur in neutrophils as they migrate from blood to joint. Methods: We performed RNA sequencing of neutrophils from healthy human blood, arthritic blood, and arthritic synovial fluid, comparing transcriptional signatures with those from murine K/BxN serum transfer arthritis. We employed mass cytometry to quantify protein expression and sought to reproduce the synovial fluid phenotype ex vivo in cultured healthy blood neutrophils. Results: Blood neutrophils from healthy donors and patients with active arthritis exhibited largely similar transcriptional signatures. By contrast, synovial fluid neutrophils exhibited more than 1,600 differentially expressed genes. Gene signatures identified a prominent response to interferon gamma (IFNγ), as well as to tumor necrosis factor, interleukin 6, and hypoxia, in both humans and mice. Mass cytometry also found healthy and arthritic donor blood neutrophils largely indistinguishable but revealed a range of neutrophil phenotypes in synovial fluid defined by downregulation of CXCR1 and upregulation of FcγRI, HLA-DR, PD-L1, ICAM-1 and CXCR4. Reproduction of key elements of this signature in cultured blood neutrophils required both IFNγ and prolonged culture. Conclusions: Circulating neutrophils from arthritis patients resemble those from healthy controls, but joint fluid cells exhibit a network of changes, conserved across species, that implicate IFNγ response and aging as complementary drivers of the synovial neutrophil phenotype.

IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets

2017 ◽  
Vol 117 (07) ◽  
pp. 1379-1390 ◽  
Author(s):  
Stefan Stojkovic ◽  
Åsa Thulin ◽  
Lena Hell ◽  
Barbara Thaler ◽  
Sabine Rauscher ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Tissue Factor ◽  
Inflammatory Diseases ◽  
Human Monocyte ◽  
Receptor Expression ◽  
Human Monocytes ◽  
Monocyte Subsets ◽  
Prothrombotic State ◽  
St2 Receptor ◽  
Classical Monocytes

SummaryMonocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NFκB-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL–33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment

2019 ◽  
Vol 4 (42) ◽  
pp. eaax8189 ◽  
Author(s):  
Marie Jo Halaby ◽  
Kebria Hezaveh ◽  
Sara Lamorte ◽  
M. Teresa Ciudad ◽  
Andreas Kloetgen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Macrophage Polarization ◽  
Suppressor Cells ◽  
Interferon Γ ◽  
Mass Cytometry ◽  
General Control ◽  
Immune Attack ◽  
Environmental Sensor ◽  
Rna Knockdown ◽  
Interfering Rna

General control nonderepressible 2 (GCN2) is an environmental sensor controlling transcription and translation in response to nutrient availability. Although GCN2 is a putative therapeutic target for immuno-oncology, its role in shaping the immune response to tumors is poorly understood. Here, we used mass cytometry, transcriptomics, and transcription factor–binding analysis to determine the functional impact of GCN2 on the myeloid phenotype and immune responses in melanoma. We found that myeloid-lineage deletion of GCN2 drives a shift in the phenotype of tumor-associated macrophages and myeloid-derived suppressor cells (MDSCs) that promotes antitumor immunity. Time-of-flight mass cytometry (CyTOF) and single-cell RNA sequencing showed that this was due to changes in the immune microenvironment with increased proinflammatory activation of macrophages and MDSCs and interferon-γ expression in intratumoral CD8+ T cells. Mechanistically, GCN2 altered myeloid function by promoting increased translation of the transcription factor CREB-2/ATF4, which was required for maturation and polarization of macrophages and MDSCs in both mice and humans, whereas targeting Atf4 by small interfering RNA knockdown reduced tumor growth. Last, analysis of patients with cutaneous melanoma showed that GCN2-dependent transcriptional signatures correlated with macrophage polarization, T cell infiltrates, and overall survival. Thus, these data reveal a previously unknown dependence of tumors on myeloid GCN2 signals for protection from immune attack.

Abstract 12944: Geographical Variations in Cardiovascular Health in China: A Nationwide Population-based Survey of 74,771 Adults

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mei Zhang ◽  
Yu Shi ◽  
Oumin Shi ◽  
Zhenping Zhao ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Health Behavior ◽  
Health Behaviors ◽  
Cardiovascular Health ◽  
Significant Heterogeneity ◽  
Chinese Adults ◽  
Ideal Cardiovascular Health ◽  
Geographical Variations ◽  
Health Factors

Background: Cardiovascular disease is the leading cause of death in China. Objectives: We aimed to evaluate the levels of cardiovascular health among Chinese adults and to understand the geographic patterns based on a nationally and provincially representative survey. Methods: In 2015, a total of 74,771 respondents aged ≥ 20 years with no history of cardiovascular disease were randomly sampled from 298 counties/districts of 31 provinces in mainland China and were interviewed. Seven metrics, including smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose, were determined. Ideal cardiovascular health was defined as the simultaneous presence of all metrics at the ideal level. A score ranging from 0 to 14 was calculated as the sum of all seven metrics for each province. Scores for four health behaviors and four health factors were also calculated. Results: The age-adjusted prevalence of ideal cardiovascular health was only 1.13% among Chinese adults above 20 years old in 2015 (0.50% among men and 1.77% among women; 1.63% among urban residents and 0.68% among rural residents). The age-adjusted prevalence varied greatly across provinces, ranging from 0.05% in Qinghai to 2.97% in Heilongjiang. Ideal diet (7.4%) was the least common among seven cardiovascular health metrics and ideal blood pressure (32.2%) was the second least one. We also saw significant heterogeneity among provinces in age-adjusted cardiovascular health score, health behavior score, and health factors score. In all provinces, women had higher scores than men for cardiovascular health, health behaviors and health factors. Differences in cardiovascular health and health behavior scores between urban and rural areas were associated with levels of socio-economic development. Conclusions: Strategies for addressing poor cardiovascular health require geographic targeting and localized consideration.

Absence of systematic relationships between REMS duration episodes and spectral power Delta and Ultra-Slow bands in contiguous NREMS episodes in healthy humans

2013 ◽  
Vol 110 (1) ◽  
pp. 162-169 ◽  
Author(s):  
O. Le Bon ◽  
P. Linkowski
Keyword(s):  
Spectral Power ◽  
Sleep Cycle ◽  
Consecutive Series ◽  
Sleep Regulation ◽  
Healthy Human ◽  
Sleep Quantity ◽  
Healthy Humans ◽  
Crucial Component ◽  
Sleep Physiology ◽  
Human Participants

Previous studies in animals and humans have reported correlations between the durations of rapid eye movement sleep (REMS) episodes and immediately preceding or subsequent non-REMS (NREMS) episodes. The relationship between these two types of sleep is a crucial component in understanding the regulation and neurophysiology of ultradian alternations that occur during sleep. Although the present study replicated previous studies, we also measured NREMS in terms of spectral power Delta and Ultra-Slow bands in addition to duration in examining correlations. The spectral power Delta band, also known as slow-wave activity, measures sleep quantity and is believed to reflect sleep physiology better than mere episode durations. The Ultra-Slow spectral power band was analyzed in parallel. Healthy human participants of both sexes ( n = 26, age range 15–45 yr, n = 12 female) were carefully selected to participate in two consecutive series of home polysomnograms performed after 2 nights of habituation to the equipment. In the analyses, REMS episode durations (minutes) were compared with immediately preceding and immediately subsequent NREMS episodes (Delta and Ultra-Slow power) in each sleep cycle. REMS episode duration was more strongly correlated with preceding NREMS episodes than with subsequent NREMS episodes. However, in most cases, no correlations were observed in either direction. One ultradian sleep regulation hypothesis, which is based on stronger correlations between REMS and subsequent NREMS episode durations, holds that the main purpose of REMS is to reactivate NREMS during each sleep cycle. The present results do not support that hypothesis.

scholarly journals Genotypic and Phenotypic Traits That Distinguish Neonatal Meningitis-Associated Escherichia coli from Fecal E. coli Isolates of Healthy Human Hosts

2012 ◽  
Vol 78 (16) ◽  
pp. 5824-5830 ◽  
Author(s):  
Catherine M. Logue ◽  
Curt Doetkott ◽  
Paul Mangiamele ◽  
Yvonne M. Wannemuehler ◽  
Timothy J. Johnson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Phylogenetic Group ◽  
Neonatal Meningitis ◽  
Phenotypic Traits ◽  
Healthy Human ◽  
Content Type ◽  
Plasmid Content ◽  
E Coli ◽  
Healthy Humans ◽  
Definition Of

ABSTRACTNeonatal meningitisEscherichia coli(NMEC) is one of the top causes of neonatal meningitis worldwide. Here, 85 NMEC and 204 fecalE. coliisolates from healthy humans (HFEC) were compared for possession of traits related to virulence, antimicrobial resistance, and plasmid content. This comparison was done to identify traits that typify NMEC and distinguish it from commensal strains to refine the definition of the NMEC subpathotype, identify traits that might contribute to NMEC pathogenesis, and facilitate choices of NMEC strains for future study. A large number ofE. colistrains from both groups were untypeable, with the most common serogroups occurring among NMEC being O18, followed by O83, O7, O12, and O1. NMEC strains were more likely than HFEC strains to be assigned to the B2 phylogenetic group. Few NMEC or HFEC strains were resistant to antimicrobials. Genes that best discriminated between NMEC and HFEC strains and that were present in more than 50% of NMEC isolates were mainly from extraintestinal pathogenicE. coligenomic and plasmid pathogenicity islands. Several of these defining traits had not previously been associated with NMEC pathogenesis, are of unknown function, and are plasmid located. Several genes that had been previously associated with NMEC virulence did not dominate among the NMEC isolates. These data suggest that there is much about NMEC virulence that is unknown and that there are pitfalls to studying single NMEC isolates to represent the entire subpathotype.

scholarly journals Capsule Formulation of Ethanolic Extract of Pasak Bumi (Eurycoma Longifolia Jack.,) and its Effect on Human Health Vital Signs

2017 ◽  
Vol 22 (2) ◽  
pp. 91
Author(s):  
Laela Hayu Nurani ◽  
Eka Kumalasari ◽  
Abdul Rohman ◽  
Sitarina Widyarini
Keyword(s):  
Bitter Taste ◽  
Vital Signs ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Inclusion Criteria ◽  
Capsule Formulation ◽  
Healthy Human ◽  
Eurycoma Longifolia ◽  
Healthy Humans ◽  
Eurycoma Longifolia Jack

Pasak bumi (Eurycoma longifolia) has the potential to be developed as antihypertensive, antipyretic, aphrodisiacs and health supplements. The use of E. longifolia as a traditional medicine needs to be pursued in the form of more effective and appropriate formulation. The capsule preparations are easy to make and cancover the bitter taste of E. longifolia. Clinical trials in this study use design pre-post treatment in healthy humans. Subjects used were male - healthy men and healthy women who met inclusion criteria and were subjected with formulated capsule for 14 days. The study resulted capsule formula comprising of the ethanolic extract of E. longifolia 300 mg, vivapur 101 300 mg, 58 mg maydis starch, aerosil 3%, talc 2%, and Mg stearate 1%. The results showed that the capsule of E. longifolia did not affect the value of heart rate, respiration rate, body temperature and weight (P > 0.05), based on paired t-test, but they causes a decrease in blood pressure of healthy human. The ethanol extract of E. longifolia caused vasodilation of blood vessels that can be used in antihypertensive therapy.

The three human monocyte subsets: implications for health and disease

2012 ◽  
Vol 53 (1-3) ◽  
pp. 41-57 ◽  
Author(s):  
Kok Loon Wong ◽  
Wei Hseun Yeap ◽  
June Jing Yi Tai ◽  
Siew Min Ong ◽  
Truong Minh Dang ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Monocyte Subsets ◽  
Health And Disease

Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Simran Grewal ◽  
Ninad Zaman ◽  
Louis Borgatta ◽  
Matthew Nudy ◽  
Brandon Peterson
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Death ◽  
Nonfatal Stroke ◽  
Significant Heterogeneity ◽  
Receptor Agonists ◽  
Meta Regression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM). Methods: RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi 2 and I 2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R 2 value was calculated. Results: 7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi 2 =12.94, p=0.04, I 2 =54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I 2 =27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R 2 =0.64, Figure 1) was observed when performing the meta-regression. Conclusion: GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.

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