Related Experiment Video
Updated: Mar 7, 2026
Quantification of Monocyte Transmigration and Foam Cell Formation from Individuals with Chronic Inflammatory Conditions
Published on: October 17, 2017
CD14+CD16++ "nonclassical" monocytes are associated with endothelial dysfunction in patients with coronary artery
Karol Urbanski, Dominik Ludew, Grzegorz Filip
1Tomasz J. Guzik, MD, PhD, FRCP, BHF Centre for Excellence, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK,
Insights
Monocyte subsets influence vascular disease. High levels of nonclassical monocytes (CD14+CD16++) and low classical monocytes (CD14++CD16-) are linked to impaired endothelial function and increased vascular superoxide production in coronary artery disease patients.
Area of Science:
- Cardiovascular Research
- Immunology
- Vascular Biology
Background:
- Endothelial dysfunction and inflammation are central to vascular disease pathogenesis.
- Monocyte heterogeneity may play a role in the development of vascular dysfunction, particularly in coronary artery disease (CAD).
Purpose of the Study:
- To investigate the relationship between distinct monocyte subsets, endothelial function, and cardiovascular risk factors in patients with CAD.
- To assess nitric oxide (NO) bioavailability and vascular superoxide production in relation to monocyte populations.
Main Methods:
- Analysis of monocyte subsets (classical, intermediate, nonclassical) using flow cytometry in 130 CAD patients.
- Ex vivo assessment of endothelial function via isometric tension studies on internal mammary arteries, measuring NO bioavailability (ACh- and SNP-dependent).
- Quantification of vascular superoxide production and expression of activation markers (CD11c) on monocytes.
Main Results:
- Patients with a high frequency of nonclassical (CD14+CD16++) monocytes and low frequency of classical (CD14++CD16-) monocytes exhibited impaired endothelial function.
- A higher proportion of nonclassical monocytes correlated with increased vascular superoxide production.
- Endothelial dysfunction was associated with elevated CD11c expression on nonclassical monocytes.
- Monocyte subset frequencies were independent predictors of endothelial dysfunction, even after accounting for major atherosclerosis risk factors.
Conclusions:
- CD14+CD16++ nonclassical monocytes are associated with more advanced vascular dysfunction, characterized by reduced NO bioavailability and increased reactive oxygen species production.
- Monocyte subset distribution is a significant factor in the pathophysiology of endothelial dysfunction in coronary artery disease.
Abstract:
Endothelial 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.
Related Concept Videos
01:26Coronary Artery Disease II: Pathophysiology
01:30Coronary Artery Disease I: Introduction