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. 2023 Jul 30;24(15):12205.
doi: 10.3390/ijms241512205.

Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients

Vadim Genkel  1 , Ilya Dolgushin  1 , Albina Savochkina  1 , Karina Nikushkina  1 , Irina Baturina  1 , Anna Minasova  1 , Veronika Sumerkina  1 , Lubov Pykhova  1 , Semen Kupriyanov  1 , Alla Kuznetsova  1 , Igor Shaposhnik  1
Affiliations

Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients

Vadim Genkel et al. Int J Mol Sci. .

Abstract

Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40-64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12-24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0-467.0 cells/μL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642-0.815) versus 0.637 (0.539-0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression.

Keywords: Toll-like receptors; atherosclerosis; immunosenescence; inflammation; intermediate monocytes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ROC curves demonstrating the diagnostic efficacy of pentraxin 3 (A) and IFNγ (B) on carotid atherosclerosis progression, TGFβ—on polyvascular atherosclerosis progression (C).
Figure 2
Figure 2
ROC curves demonstrating the diagnostic efficacy of T-regulatory lymphocytes in relation to carotid atherosclerosis progression (A), TLR4-positive classical monocytes in relation to lower limb arterial atherosclerosis progression (B), TLR4-positive intermediate monocytes in relation to lower limb artery atherosclerosis (C), and polyvascular (D) atherosclerosis progression.
Figure 3
Figure 3
TGFβ, IL7, GM-CSF, TNFα, IL6, IL8 concentration in relation to the presence of generalized polyvascular atherosclerosis. Pairwise comparisons were performed using the Mann–Whitney test.
Figure 4
Figure 4
T-regulatory lymphocyte levels as a function of atherosclerosis extent (A) and the presence of generalized polyvascular atherosclerosis (B). Comparisons between the five groups (A) were made using the Kruskal–Wallis test, followed by post hoc Dunn’s test with the Bonferroni significance level correction. Pairwise comparisons (B) were performed using the Mann–Whitney test.
See this image and copyright information in PMC

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