- [Show abstract] [Hide abstract] ABSTRACT: AimsMonocytes and monocyte-derived macrophages have been recognised as the cellular hallmark of atherosclerosis decades ago. Recently, they have also been shown to play a pivotal role in obesity. Monocytes display immunophenotypic heterogeneity with functionally distinct subpopulations. We initiated the I LIKE HOMe study to examine monocyte heterogeneity in obesity and subclinical atherosclerosis.Methods and resultsWe assessed carotid intima media thickness (IMT), body mass index (BMI), and other cardiovascular risk factors in 622 healthy volunteers. Using flow-cytometry, we differentiated monocytes into CD14++CD16- and CD16+ cells, which we further subdivided into CD14++CD16+ and CD14 (+)CD16+ cells. Body mass index was significantly correlated with carotid IMT. High CD16+ monocyte counts were significantly associated with both higher BMI and increased carotid IMT. Adjustment for CD16+ monocyte counts weakened the correlation between BMI and carotid IMT, suggesting that the increase in CD16+ monocyte numbers in obesity may partly explain the association between obesity and IMT.Conclusion Our results reveal a significant univariate association between CD16+ monocytes and both obesity and subclinical atherosclerosis in low-risk individuals. They are in line with recent observations that CD16 + monocytes show high endothelial affinity and a potent capacity to invade vascular lesions and to transform into pro-inflammatory cytokine producing macrophages.
- [Show abstract] [Hide abstract] ABSTRACT: Haemodialysis with bioincompatible membranes led to transient leukocyte activation and intra-dialytic leukopenia due to endothelial adherence. After the introduction of biocompatible membranes, only CD16(+) (i.e. CD14(++)CD16(+) and CD14((+))CD16(+)) monocytes showed an impressive transient intra-dialytic decrease. Presently, it is unclear whether this CD16(+) monocyte drop is detrimental. We investigated whether a prominent intra-dialytic decrease of CD16(+) monocytes predicts future cardiovascular (CV) events. We measured leukocyte and monocyte subpopulations in 70 patients before and 10 min after haemodialysis initiation. Patients were stratified by their intra-dialytic CD14(++)CD16(+) monocyte drop (pre-defined major drop: decline of cell counts at 10 min to <50% of pre-dialytic values; pre-defined minor drop: decline to values >50% of pre-dialytic counts). Patients were followed up for 42 +/- 2 months; endpoints were CV events and death. Patients with a minor CD14(++)CD16(+) monocyte drop had more CV events than patients with a major drop. In multivariate analysis, a minor CD14(++)CD16(+) monocyte drop was the strongest independent predictor of future CV events [hazard ratio 2.405 (95% CI 1.192-4.854)]. These data refute the assumption that a prominent intra-dialytic decrease of CD14(++)CD16(+) monocytes is detrimental. Instead, a minor cell drop could mirror CD14(++)CD16(+) monocyte dysfunction, with inadequate migratory reaction towards an immunologic stimulus posed by membrane and tubing contact.