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Thromb Haemost 2017; 117(05): 971-980
DOI: 10.1160/TH16-08-0614
Blood Cells, Inflammation and Infection
Schattauer GmbH

CD14+CD16++ “nonclassical” monocytes are associated with endothelial dysfunction in patients with coronary artery disease

Karol Urbanski
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Dominik Ludew
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Grzegorz Filip
2   Department of Cardiovascular Surgery and Transplantation, Institute of Cardiology, Jagiellonian University Collegium Medicum, Krakow, Poland
,
Magdalena Filip
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Agnieszka Sagan
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
3   British Heart Foundation Centre for Excellence, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
,
Piotr Szczepaniak
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Grzegorz Grudzien
2   Department of Cardiovascular Surgery and Transplantation, Institute of Cardiology, Jagiellonian University Collegium Medicum, Krakow, Poland
,
Jerzy Sadowski
2   Department of Cardiovascular Surgery and Transplantation, Institute of Cardiology, Jagiellonian University Collegium Medicum, Krakow, Poland
,
Barbara Jasiewicz-Honkisz
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Tomasz Sliwa
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
,
Boguslaw Kapelak
2   Department of Cardiovascular Surgery and Transplantation, Institute of Cardiology, Jagiellonian University Collegium Medicum, Krakow, Poland
,
Eilidh McGinnigle
3   British Heart Foundation Centre for Excellence, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
,
Tomasz Mikolajczyk
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
3   British Heart Foundation Centre for Excellence, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
,
Tomasz J. Guzik
1   Translational Medicine Laboratory, Department of Internal Medicine, Jagiellonian University, Collegium Medicum, Krakow, Poland
3   British Heart Foundation Centre for Excellence, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland, UK
› Author Affiliations Financial support: The research was funded by budget resources for science in 2012–2016 as MNISW “Diamond Grant” (DI2011 022241), National Science Centre (Nr 2011/03/B/NZ4/02454 and Nr 2015/19/N/NZ5/02262) and BHF Centre of Research Excellence (RE/13/5/30177). “Mobilnosc Plus” supported some work on the revision (1280/MOB/IV/2015/0 to TM and 1079/MOB/2013/0 and 1079/1/MOB/13/2014/0 to AS).
Further Information

Publication History

Received: 09 August 2016

Accepted after major revision: 23 January 2016

Publication Date:
28 November 2017 (online)

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Summary

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.

Keywords

Endothelial dysfunction - monocytes - ischaemic heart disease - atherosclerosis

 

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