scholarly journals Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease

2018 ◽  
Author(s):  
Kathryn A. Arnold ◽  
John E. Blair ◽  
Jonathan D. Paul ◽  
Atman P. Shah ◽  
Sandeep Nathan ◽  
...  

ABSTRACTBackground: 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 (CD14loCD16hi) 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.

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044054
Author(s):  
Victoria McCreanor ◽  
Alexandra Nowbar ◽  
Christopher Rajkumar ◽  
Adrian G Barnett ◽  
Darrel Francis ◽  
...  

ObjectiveTo evaluate the cost-effectiveness of percutaneous coronary intervention (PCI) compared with placebo in patients with single-vessel coronary artery disease and angina despite anti-anginal therapy.DesignA cost-effectiveness analysis comparing PCI with placebo. A Markov model was used to measure incremental cost-effectiveness, in cost per quality-adjusted life-years (QALYs) gained, over 12 months. Health utility weights were estimated using responses to the EuroQol 5-level questionnaire, from the Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial and UK preference weights. Costs of procedures and follow-up consultations were derived from Healthcare Resource Group reference costs and drug costs from the National Health Service (NHS) drug tariff. Probabilistic sensitivity analysis was undertaken to test the robustness of results to parameter uncertainty. Scenario analyses were performed to test the effect on results of reduced pharmaceutical costs in patients undergoing PCI, and the effect of patients crossing over from placebo to PCI due to refractory angina within 12 months.SettingFive UK NHS hospitals.Participants200 adult patients with stable angina and angiographically severe single-vessel coronary artery disease on anti-anginal therapy.InterventionsAt recruitment, patients received 6 weeks of optimisation of medical therapy for angina after which they were randomised to PCI or a placebo procedure.Outcome measuresIncremental cost-effectiveness ratio (ICER) expressed as cost (in £) per QALY gained for PCI compared with placebo.ResultsThe estimated ICER is £90 218/QALY gained when using PCI compared with placebo in patients receiving medical treatment for angina due to single-vessel coronary artery disease. Results were robust under sensitivity analyses.ConclusionsThe ICER for PCI compared with placebo, in patients with single-vessel coronary artery disease and angina on anti-anginal medication, exceeds the threshold of £30 000 used by the National Institute of Health and Care Excellence when undertaking health technology assessment for the NHS context.Trial registration: The ORBITA study is registered with ClinicalTrials.gov, number NCT02062593.


2015 ◽  
Vol 241 (1) ◽  
pp. e94
Author(s):  
M. Schmid ◽  
J. Marti-Jaun ◽  
M. Bühler ◽  
M. Herová ◽  
M. Hersberger

2018 ◽  
Vol 71 (11) ◽  
pp. A158
Author(s):  
Kathryn Arnold ◽  
John Blair ◽  
Jonathan Paul ◽  
Atman Shah ◽  
Sandeep Nathan ◽  
...  

2020 ◽  
Vol 11 (6) ◽  
pp. 68-71
Author(s):  
Binay Kumar Rauniyar ◽  
Arun Kadel ◽  
Kiran Prasad Acharya ◽  
Kartikesh Kumar Thakur ◽  
Rakesh Bahadur Adhikari ◽  
...  

Background: With rise in prevalence of conventional risk factors like diabetes, hypertension, smoking, dyslipidemia and obesity the incidence of coronary artery disease in young patients have increased in the recent decades even in developing world. There have been multiple studies done in Nepal studying the angiographic profile of coronary disease in general population. However, only few studies has been done till date on the angiographic profile in the young population in our country. Aims and Objectives: In this study, we aim to determine the angiographic profile of young patient ≤ 40 years in a tertiary care centre of Nepal. Materials and Methods: A retrospective analytic study was done in Shahid Gangalal National Heart Centre from January 2019 to December 2019. Individuals of both genders with age ≤ 40 years who underwent coronary angiography were included. Results: Total 109 patients were included. Out of 109, 89 were male and 20 were female. The mean age for male was 35.55 ± 4.31 and for female was 38.55 ± 1.90 (P = 0.003). Among 61 (55.96%) patients who had significant coronary artery disease, 33 patients (30.27%) with single vessel disease, 15 patients (13.76%) had double vessel disease, and 13 patients (11.92%) had triple vessel disease. Left anterior descending (LAD) artery was found to be most frequently involved in all patterns of Coronary artery disease (CAD). Smoking was the most common coronary risk factor present in 29.3% of patients followed by hypertension, family history of premature CAD and diabetes in 14.6%, 7.5% and 5.5% of patients respectively. Overall, the prevalence of smoking was more in males (31.4%) than in females (20%). Conclusion: Single vessel disease (SVD) was most prevalent in young patients with significant CAD. LAD is the most commonly involved coronary artery followed by Right coronary artery (RCA) and Left Circumflex (LCX).


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Marlies P Noz ◽  
Siroon Bekkering ◽  
Laszlo Groh ◽  
Tim MJ Nielen ◽  
Evert JP Lamfers ◽  
...  

Atherosclerosis is the major cause of cardiovascular disease (CVD). Monocyte-derived macrophages are the most abundant immune cells in atherosclerotic plaques. In patients with atherosclerotic CVD, leukocytes have a hyperinflammatory phenotype. We hypothesize that immune cell reprogramming in these patients occurs at the level of myeloid progenitors. We included 13 patients with coronary artery disease due to severe atherosclerosis and 13 subjects without atherosclerosis in an exploratory study. Cytokine production capacity after ex vivo stimulation of peripheral blood mononuclear cells (MNCs) and bone marrow MNCs was higher in patients with atherosclerosis. In BM-MNCs this was associated with increased glycolysis and oxidative phosphorylation. The BM composition was skewed towards myelopoiesis and transcriptome analysis of HSC/GMP cell populations revealed enrichment of neutrophil- and monocyte-related pathways. These results show that in patients with atherosclerosis, activation of innate immune cells occurs at the level of myeloid progenitors, which adds exciting opportunities for novel treatment strategies.


2017 ◽  
Vol 117 (05) ◽  
pp. 971-980 ◽  
Author(s):  
Karol Urbanski ◽  
Dominik Ludew ◽  
Grzegorz Filip ◽  
Magdalena Filip ◽  
Agnieszka Sagan ◽  
...  

SummaryEndothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14++CD16– “classical – Mon1”, CD14++CD16+ “intermediate – Mon2” and CD14+CD16++ “nonclassical – Mon3”), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium- nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14+CD16++ “nonclassical” and low CD14++CD16- “classical” monocytes presented impaired endothelial function. High frequency of CD14+CD16++ “nonclassical” monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14+CD16++ monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β =0.18 p=0.04 and β =-0.19 p=0.03, respectively). In summary, our data indicate that CD14+CD16++ “nonclassical” monocytes are associated with more advanced vascular dysfunction measured as NO-bioavailability and vascular reactive oxygen species production.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Liu ◽  
C G Zhu ◽  
C J Cui ◽  
Y X Cao ◽  
D I Sun ◽  
...  

Abstract Abstract Background Inflammation may play an important role in atherosclerosis in familial hypercholesterolemia (FH). Lipopolysaccharide (LPS)-nuclear factor-kappa B (NF-κB) pathway is a routine signal process activated in inflammatory status. Purpose This study aimed to examine the LPS-NF-κB axis status and the impact of lipoprotein apheresis (LA) on this pathway in patients with FH and coronary artery disease (CAD). Methods In this matched case-control study a genetically diagnosed FH cohort who presented stable CAD (n=63) was compared with 63 non-FH CAD and 63 non-FH non-CAD controls matched by sex and age. Plasma LPS levels and NF-κB activity were compared among the three groups. In addition, we studied in vitro LPS-induced interleukin-6 (IL-6) production by mononuclear cells from 16 FH cases without previous statin use and compared them with their respective matched control groups. Subsequently, these 16 FH patients underwent LA. Blood samples were taken immediately before and regularly after LA for measuring LPS and NF-κB. Results FH plus CAD had higher LPS levels and NF-κB activity than CAD and non-CAD controls (all p values <0.01). LPS-induced IL-6 production by mononuclear cells of FH plus CAD was also much higher compared with CAD and non-CAD controls (both p values <0.01). Moreover, plasma LPS levels (p<0.001) and NF-κB activity (p<0.01) were dramatically reduced after apheresis in FH patients. Conclusion Genetically confirmed FH patients with CAD had a marked activation of LPS-NF-κB axis, while LA significantly attenuated this key inflammatory pathway, suggesting that inflammation may be an important therapeutic target for FH patients.


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