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. 2023 Oct 27;11(11):2911.
doi: 10.3390/biomedicines11112911.

Intermediate Monocytes and Circulating Endothelial Cells: Interplay with Severity of Atherosclerosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus

Irina V Kologrivova  1 , Tatiana E Suslova  1 , Olga A Koshelskaya  1 , Elena S Kravchenko  1 , Olga A Kharitonova  1 , Ekaterina A Romanova  2 , Alexandra I Vyrostkova  2 , Alla A Boshchenko  1
Affiliations

Intermediate Monocytes and Circulating Endothelial Cells: Interplay with Severity of Atherosclerosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus

Irina V Kologrivova et al. Biomedicines. .

Abstract

The aim was to investigate the association of monocyte heterogeneity and presence of circulating endothelial cells with the severity of coronary atherosclerosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). We recruited 62 patients with CAD, including 22 patients with DM2. The severity of atherosclerosis was evaluated using Gensini Score. Numbers of classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) monocyte subsets; circulating endothelial progenitor cells; and the presence of circulating endothelial cells were evaluated. Counts and frequencies of intermediate monocytes, but not glycaemia parameters, were associated with the severity of atherosclerosis in diabetic CAD patients (rs = 0.689; p = 0.001 and rs = 0.632; p = 0.002, respectively). Frequency of Tie2+ cells was lower in classical than in non-classical monocytes in CAD patients (p = 0.007), while in patients with association of CAD and T2DM, differences between Tie2+ monocytes subsets disappeared (p = 0.080). Circulating endothelial cells were determined in 100% of CAD+T2DM patients, and counts of CD14++CD16+ monocytes and concentration of TGF-β predicted the presence of circulating endothelial cells (sensitivity 92.3%; specificity 90.9%; AUC = 0.930). Thus, intermediate monocytes represent one of the key determinants of the appearance of circulating endothelial cells in all the patients with CAD, but are associated with the severity of atherosclerosis only in patients with association of CAD and T2DM.

Keywords: TGF-beta; atherosclerosis; circulating endothelial cells; coronary artery disease; endothelial progenitor cells; monocytes; type 2 diabetes mellitus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Gating strategy for monocytes subset: (a) gating of classical (CD14++CD16–), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes: identification of cells in focus; single cells; monocytes via parameters of area and side scatter; exclusion of CD16+HLA-DR– cells; identification of regions for monocytes subsets; (b) representative images of classical (CD14++CD16–), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes; (c) identification of Tie2+ monocytes; (d) identification of HLA-DR+ monocytes.
Figure 2
Figure 2
Gating strategy for circulating endothelial cells: (a) gating of CD45– cells: identification of cells in focus; single cells; peripheral blood mononuclear cells via parameters of area and side scatter; identification of CD45– cells; (b) gating of CD45–CD146+ cells; (c) verification of circulatory endothelial cells using image gallery—only one cell out of several gated cells represents circulatory endothelial cell based on cellular morphology and expression of specific endothelial markers.
Figure 3
Figure 3
Gating strategy for endothelial progenitor cells: (a) gating of cells in focus; single cells; peripheral blood mononuclear cells via parameters of area and intensity of autofluorescence in brightfield channel; identification of CD34+CD45dim cells; identification of CD34+CD45dimCD133+ cells; identification of CD34+CD45dimCD133+CD31+ cells; (b) representative images of endothelial progenitor cells.
Figure 4
Figure 4
Tie2+ expression on monocyte subsets in patients with coronary artery disease depending on the presence of type 2 diabetes mellitus.
Figure 5
Figure 5
Presence of circulating endothelial cells in groups of patients.
Figure 6
Figure 6
ROC curve of the multiple logistics regression for classification of patients into groups with presence or absence of circulating endothelial cells.
See this image and copyright information in PMC

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