Background: Myocardial infarction complicated by cardiogenic shock (MI-CS) remains a critical condition with high mortality rates, despite advances in treatment. Systemic inflammation plays a significant role in MI-CS progression; however, its dynamics across different stages of the Society for Cardiovascular Angiography and Interventions (SCAI) classification remain poorly understood. This study aimed to evaluate indices of systemic inflammation—neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI)—in MI-CS patients, correlating them with SCAI stages and survival outcomes. Methods: A single-center retrospective study included 132 patients with MI-CS, categorized into SCAI stages A–E. All patients were assessed for demographic, clinical, and laboratory data, procedural and treatment characteristics, MI timing, and outcomes. Complete blood count test data were used to calculate inflammatory indices and evaluate types of immune reactions. Results: PLR, SII, and AISI peaked at SCAI stage C and declined significantly at stage E, suggesting suppressed inflammation in advanced shock. SIRI emerged as a key prognostic marker for stage C patients, with elevated levels associated with larger infarct size, higher heart rate, and predominant innate immune activation. Patients with SIRI ≥ 3.34 had significantly lower two-year survival (log-rank test, p = 0.006). Conclusions: Inflammation indices, particularly SIRI, provide valuable prognostic insights in MI-CS, reflecting disease severity and heterogeneity of immune response. The decline in inflammatory indices at SCAI stage E may indicate immune suppression in extreme MI-CS, underscoring the need for personalized therapeutic strategies.

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with CAD. Methods: A single-center, cross-sectional, comparative study was conducted. Patients were stratified according to the severity of coronary atherosclerosis: patients with a Gensini score ≥ 65 points and patients with a Gensini score < 65 points. Peripheral blood and thymus biopsy were obtained. Imaging flow cytometry, ELISA, and immunohistochemical analysis were used for analysis. Results: Thymic morphology ranged from total fatty involution to a preserved structure of the thymus (20–80% area in 31% of obtained samples) but was not associated with the severity of atherosclerosis. Meanwhile, patients with a Gensini score ≥ 65 had impaired thymus cellular composition compared to patients with a Gensini score < 65 points; increased frequency of CD8+ T lymphocytes and NK cells; and decreased frequency of CD4 + CD8+ T lymphocytes. In peripheral blood, the main determinants of a Gensini score ≥ 65 points were low absolute counts of eMDSCs and CD25^low Tregs with FoxP3 nuclear translocation, while advanced vascular aging was associated with elevated eMDSC absolute counts. Advanced coronary atherosclerosis was also associated with decreased numbers of endothelial progenitor cells in circulation. Conclusions: Thymus dysfunction accompanies CAD progression and is manifested in changes in cellular composition rather than morphology. In CAD patients, MDSC and Treg lymphocytes are equally involved in the progression of coronary atherosclerosis, which is aggravated by the decreased regulatory potential of the endothelium. Vascular aging represents a distinct phenotype of biological aging in CAD patients, characterized by the expansion of eMDSCs.

BACKGROUND: One of the common pathogenic links of diabetes mellitus type 2 (T2DM) and coronary artery disease (CAD) is chronic low-grade inflammation, restricted by FoxP3+ T-regulatory lymphocytes.AIM: To investigate the numbers of FoxP3+CD25^hi and FoxP3+CD25^lo T-lymphocytes, the subcellular localization of FoxP3 in them, and the production of the main cytokines in relation to clinical and metabolic parameters in patients with association of CAD and T2DM.MATERIALS AND METHODS: An observational single-center single-stage comparative study was conducted. The severity of atherosclerosis was assessed by calculating the Gensini Score index after coronary angiography. Absolute numbers and frequencies of CD4+CD25^hiFoxP3+ and CD4+CD25^loFoxP3+ T-lymphocytes were assessed in peripheral blood by flow cytometry. Imaging flow cytometry was used to determine the degree of FoxP3 translocation to the cell’s nucleus. Concentration of cytokines in blood serum and supernatants of mononuclear leukocytes’ cultures was determined by the multiplex analysis.RESULTS: We recruited 57 patients with chronic CAD. Of these, T2DM was diagnosed in 22 patients. In patients with CAD and T2DM, the absolute numbers and frequencies of FoxP3+CD25^lo cells were increased compared to patients with CAD without diabetes (1.15 (0.98; 1.73) vs. 0.96 (0.60; 1.15)% (р=0.046); 1.48 (1.05; 1.97) vs. 1.07 (0.71; 1.42) x10⁷/L (р=0.025)). Patients with T2DM also had a higher level of translocation of FoxP3 to the nucleus of FoxP3+CD25lo cells (92.0 (86.4; 95.0) vs. 88.7 (80.0; 91.4)%, р=0.040) and increased concentration of the chemokine CCL22 both in blood serum (912 (828; 1061) vs. 669 (585; 738) pg/mL, р=0.022) and supernatants of LPS-stimulated mononuclear leukocyte cultures (1189 (851; 1310) vs. 539 (437; 949) pg/mL, р=0.038), which correlated with the presence of CD4+CD25^hiFoxP3+ cells (Rs=0.587; p=0.044) and the triglyceride/glucose index (Rs=0.587; p=0.044). The identified changes were most pronounced in patients with moderately elevated values on the Gensini Score (17–45 points).CONCLUSION: We are the first to show association between the numbers of FoxP3+CD25^lo-lymphocytes in peripheral blood and an increase in the nuclear translocation of FoxP3 in them with the severity of atherosclerosis in patients with association of CAD and T2DM. These data justify the necessity of the further investigation of the diagnostic significance of FoxP3+CD25^lo-cells as biomarkers of tissue inflammation.

T regulatory lymphocytes (Treg) are present is adipose tissue. Their frequency, as well as the level of FoxP3 nuclear translocation, in epicardial and thymus adipose tissue remains unexplored. Properties of adiposeresident Tregs may be of high significance in patients with coronary artery disease as potential pathophysiological factor in the development of atherosclerosis. The aim of the study was to compare frequency of FoxP3⁺Tregs and FoxP3 nuclear translocation in epicardial, thymus, subcutaneous adipose tissue and peripheral blood in patients with coronary artery disease. A pilot study was conducted in 11 patients with coronary artery disease scheduled for the coronary artery bypass graft surgery after prior selective coronary angiography. Frequency of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes and FoxP3 nuclear translocation were evaluated by imaging flow cytometry in peripheral blood and in stromal vascular fraction of epicardial, subcutaneous and thymus adipose tissue. Frequencies of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes were higher in epicardial adipose tissue compared to blood (3 and 5 times higher, p = 0.020); CD4⁺CD25^loFoxP3⁺ cells frequency in subcutaneous adipose tissue was 4 times higher than in blood (p = 0.028). The level of FoxP3 nuclear translocation was the highest in blood and decreased in epicardial, subcutaneous and thymus adipose tissue (p = 0.020 both for CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ lymphocytes). Frequency of CD4⁺CD25^loFoxP3⁺ cells was directly related to age in thymus (r_s = 0.818; p = 0.002), and inversely in epicardial adipose tissue (r_s = -0.618; p = 0.043). Frequencies of CD4⁺CD25^hiFoxP3⁺ and CD4⁺CD25^loFoxP3⁺ with FoxP3 nuclear translocation in subcutaneous adipose tissue negatively correlated with age (r_s = -0.827; p = 0.002 and r_s = -0.648; p = 0.031, respectively). Frequency of CD4⁺CD25^loFoxP3⁺ cells with FoxP3 nuclear translocation in thymus adipose tissue negatively correlated with waist-to-hip ratio (r_s = -0.700; p = 0.016). The severity of atherosclerosis was related only to the frequency of CD4⁺CD25^loFoxP3⁺ cells in subcutaneous adipose tissue (r_s = -0.655; p = 0.029). Thus, epicardial and subcutaneous adipose tissue are enriched with Tregs, but factors that influence Treg accumulation and FoxP3 nuclear translocation in these fat depots may be different. The obtained results may further be used for personalized immunomodulatory therapy in patients with atherosclerosis.

BACKGROUND: Chronic subclinical inflammation caused by coronary atherosclerosis (CA) can be assessed more accurately using local biomarkers, such as regulatory T cells (Tregs) of epicardial (EAT) and thymic adipose tissue (TAT). However, this approach is limited by the high invasiveness, which requires the development of alternative methods for evaluating Treg markers. Among the available diagnostic procedures, multi-slice computed tomography (MSCT) has emerged as a valuable tool, offering a comprehensive assessment of the EAT parameters. AIM: This study aimed to examine the correlation of the characteristics of FoxP3+ regulatory T cells in peripheral blood, EAT, TAT, and subcutaneous adipose tissue (SAT) with MSCT findings of the EAT in high-risk patients with coronary atherosclerosis of varying severity. METHODS: The study included 20 patients with high cardiovascular risk, who were divided into groups based on their Gensini Scores (GS): severe CA group (GS 26.5; n = 13) and moderate CA group (GS 26.5; n = 7). The FoxP3 nuclear translocation and levels of CD4+CD25hiFoxP3 and CD4+CD25loFoxP3 Tregs were measured by flow cytometry and visualized in EAT, TAT, SAT, and peripheral blood. The volume and density of the EAT were assessed using MSCT. RESULTS: In the moderate CA group, a lower proportion of CD4+CD25hiFoxP3 Tregs was found in the TAT (6.12% [3.77%; 12.00%] vs. 13.5% [7.48%; 17.4%], p = 0.046). In the severe CA group, correlations were identified between the EAT density and the FoxP3 nuclear translocation for CD4+CD25hiFoxP3 Tregs in the TAT (rs = –0.63; p = 0.021) and CD4+CD25loFoxP3 Tregs in the SAT (rs = –0.58; p = 0.036). The findings demonstrate a notable bidirectional correlation between the FoxP3 nuclear translocation for CD4+CD25hiFoxP3 Tregs in the EAT and the EAT density in patients with varying severity of atherosclerosis (GS ≤26.5; rs = 0.79; p = 0.035 vs. GS 26.5; rs = –0.71; p = 0.006). In the peripheral blood of the severe CA group, a correlation was identified between the proportion of CD4+CD25loFoxP3 Tregs and the EAT volume (rs = –0.60; p = 0.006). CONCLUSIONS: The severe CA group demonstrated a series of inverse correlations between the EAT density and the FoxP3 nuclear translocation for all fat depots. These findings suggest a reduction in the immunosuppressive potential of Tregs in the context of CA progression. The results also indicate the viability of MSCT for the indirect assessment of the immunosuppressive potential of this cell population.

Introduction. T-regulatory (T-reg) lymphocytes as the main modulators of immunity, present in ectopic adipose tissue focuses, may be involved in the pathogenesis of atherosclerosis. Currently there is a lack of data regarding T-reg lymphocyte counts, particularly in epicardial (EAT) and thymic adipose tissue (TAT) in patients with coronary atherosclerosis.Aim: To study the contents of FoxP3+ T-regulatory lymphocytes of peripheral blood, epicardial and thymic adipose tissue in patients with coronary atherosclerosis.Materials and Methods. The study included a total of 26 cardiosurgical profile patients with coronary atherosclerosis. Patients were divided into two groups via Gensini Score (GS): first group with severe coronary atherosclerosis (GS > 26.5; n = 15) and second group without severe coronary atherosclerosis (GS ≤ 26.5; n = 11). In all patients, the levels of FoxP3 nuclear translocation and the relative content of CD4+CD25^hiFoxP3 and CD4+CD25^loFoxP3 T-reg lymphocytes in peripheral blood, epicardial, thymic, and subcutaneous adipose tissue (SAT) were determined by flow cytometry with imaging.Results. The group of patients with severe coronary atherosclerosis was characterised by a statistically significant higher median of relative content of CD4+CD25^hiFoxP3 T-lymphocytes (12.0 (6.5; 17.4) vs. 6.82 (3.32; 12.4) %; p = 0.031) and statistically significant lower median of nuclear translocation level of FoxP3 in CD4+CD25^hiFoxP3 T-lymphocytes in TAT (30.82 (18.50; 40.80) vs. 51.91 (25.9; 71.00) %; p = 0.048). Statistically significant correlations between FoxP3 T-reg lymphocyte parameters in different adipose depots and lipid spectrum markers (TC, HDL-C) were found. There were inverse correlations found between EAT and TAT, in particular, between the relative contents of T-reg lymphocytes and of the FoxP3 nuclear translocation level.Conclusion. Patients with severe coronary atherosclerosis (GS > 26.5 points) were characterised by an increased relative content of CD4+CD25^hiFoxP3 T-lymphocytes in thymic adipose tissue and a decreased level of FoxP3 nuclear translocation in this cell subpopulation compared to patients with moderate atherosclerosis (GS ≤ 26.5 points). Identified correlations between relative content of T-reg lymphocytes and the level of FoxP3 nuclear translocation in thymic and epicardial adipose tissues suggest potential existence of T-reg lymphocyte recirculation in-between these ectopic adipose depots.