Increased proatherogenic monocyte–platelet cross-talk in monocyte subpopulations of patients with stable coronary artery disease
Article first published online: 30 OCT 2013
© 2013 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 275, Issue 2, pages 144–154, February 2014
How to Cite
University Medical Center Göttingen, Göttingen, Germany. Increased proatherogenic monocyte–platelet cross-talk in monocyte subpopulations of patients with stable coronary artery disease. J Intern Med 2014; 275: 144–154., , , , ,
- Issue published online: 17 JAN 2014
- Article first published online: 30 OCT 2013
- Accepted manuscript online: 11 OCT 2013 02:30AM EST
- Heidenreich von Siebold-Programm
- University Medical Center Göttingen
- coronary artery disease;
- monocyte–platelet aggregates;
Monocytes and platelets are important cellular mediators of atherosclerosis. Human monocytes can be divided into CD14++CD16−, CD14++CD16+ and CD14+CD16++ cells, which differ in their functional properties. The aim of this study was to examine monocyte subset distribution, monocyte–platelet aggregate (MPA) formation and expression of CCR5, the receptor of the platelet-derived chemokine CCL5, and to determine whether these parameters are altered in individuals with coronary atherosclerosis.
Peripheral blood cells from 64 healthy blood donors (HBDs) and 60 patients with stable coronary artery disease (CAD) were stained with antibodies against CD14, CD16, CD42b and CCR5 and analysed by flow cytometry. Circulating CCL5 levels were determined using an enzyme-linked immunosorbent assay.
In patients with CAD, the relative proportion of the CD14++CD16− monocyte subset was elevated (P < 0.05) and of the CD14+CD16++ subset was reduced (P < 0.001) compared with the HBD group. Furthermore, MPA formation significantly increased in patients with CAD in all three monocyte subsets. In both study groups, the majority of CCR5+ cells was detected in CD14++CD16+ monocytes (P < 0.001 versus CD14++CD16− and CD14+CD16++), although the CCR5+ monocyte number was reduced in patients with CAD (CD14++CD16−/CD14+CD16++, P < 0.001; CD14++CD16+, P < 0.05) compared with the HBD group, particularly in those who were not taking statins. Ex vivo incubation of monocytes from HBDs with plasma from patients with CAD also decreased CCR5+ expression (P < 0.05 versus plasma from HBDs). Serum CCL5 levels were similar in both groups.
The increased monocyte–platelet cross-talk in patients with CAD might have contributed to atherosclerosis progression. The decreased CCR5+ monocyte numbers in patients with CAD could have resulted from CCR5+ cell recruitment into atherosclerotic lesions or CCR5 downregulation in response to circulating factors.