Научная статья на тему 'PECULIARITIES OF CELLULAR IMMUNITY IN ATHEROSCLEROSIS'

PECULIARITIES OF CELLULAR IMMUNITY IN ATHEROSCLEROSIS Текст научной статьи по специальности «Фундаментальная медицина»

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Похожие темы научных работ по фундаментальной медицине , автор научной работы — Filatova A. Yu.

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Текст научной работы на тему «PECULIARITIES OF CELLULAR IMMUNITY IN ATHEROSCLEROSIS»

СБОРНИК ТЕЗИСОВ

048-049

considered to be preserved by more than 50%. The following indicators of myocardial work were evaluated: global myocardial work index (GWI), which is calculated as the contour area, global constructive work (GCW, mm Hg%) — the sum of the work of all segments performed during fiber shortening in the systole and negative work during elongation in the isovolumetric relaxation phase, global wasted work (GWW, mm Hg%) — the sum of the negative work of all segments during elongation in the systole and positive work of all segments during diastole shortening, global work efficiency (GWE) — calculated as GCW/ (GCW+GWW), %. Heart failure was confirmed by a 6-minute walk test performed 6 months after the index event. The values are presented as mean and 95% confidence intervals (CI).

Results. 6 months after STEMI, 26 people registered a value of FV>50% (HFpEF), (58,3% [56,1; 60,5]). The average value of FV in KG was 60,8% [59,3; 62,1] and did not significantly differ from the indicators of the HFpEF group. In the group of patients with HFpEF, the average distance traveled in 6 minutes was 410,7 m [95% CI 378,9; 442,5], which corresponds to the NYHA FC II. Standard echocardiography parameters had the following values: EDV 122.5 [95% CI 104.4; 140,7], in CG-104,7 [95% CI 97,6; 111,8] (p<0,05); ESV 83,8 [95% CI 28,5; 139], in KG-42 [95% CI 38,6; 45,5] (p<0,05); LVMI 89,3 [95% CI 77,4; 101,1], in CG — 65,2 [95% CI 60,9; 69,5] (p<0,05); RWT 0,37 [95% CI 0,33; 0,4] in CG — 0,36 [95% CI 0,33; 0,39] (p>0,05). GWI was 1913 [95% CI 1750; 2076], in CG — 2138,4 [95% CI 2046; 2230,8] (p<0,05), GCW — 2145,5 [95% CI 1965,8; 2325,1] and 2436,5 [95% CI 2342,7; 2530,2] (p<0,05), respectively, GWW — 75,4 [95% CI 54,1; 96,8] and 70,1 [95% CI 53,4; 86,9] (p>0,05), GWE — 95,4 [95% CI 94; 96,7] and 96,5 [95% CI 95,8; 97,3] in the corresponding groups (p<0,05).

Conclusion. Thus, the indicators of myocardial function, except for GWW, had lower values in patients with HFpEF in contrast to healthy ones, despite the satisfactory values of EF.

048 PECULIARITIES OF CELLULAR

IMMUNITY IN ATHEROSCLEROSIS

Filatova A. Yu.

National Medical Research center of cardiology, Moscow, Russia.

Aim. The study aimed to analyze the content and functional activity of circulating pro- and anti-inflammatory subpopulations of lymphocytes and monocytes in the blood of patients with atherosclerosis of the coronary and carotid arteries to identify the individuals prone to the rapid progression of atherosclerotic disease; to evaluate the immunotropic effects of statins in vitro and the influence of statin intake on the parameters of cellular immunity in vivo.

Material and methods. 220 patients with different severity of coronary and carotid atherosclerosis were enrolled. Dynamic coronary angiography and carotid ultrasound were used for atherosclerosis verification and progression. Cell phenotyping was performed in blood samples and mononuclear leukocyte culture using direct immunofluorescence and flow cytometry. Activated T-helper (Th) cells were identified as CD4+CD25lowCD127high, regulatory T-cells (Treg) as CD4+CD25highCD127low and CD4+Foxp3+, IL10-producing T-cells as CD4+IL10+, Th17 as CD4+IL17a+, Th1 as CD4+INFy+. Monocytes were identified as classical (CD14++CD16-), intermediate (CD14++CD16+) and nonclassical (CD14+CD16++). The effects of statins were studied in the cultures of CD4+ T-lymphocytes and macrophages (Mph) differentiated from blood CD14+monocytes using GM-CSF and activated with LPS/INFy. CFSE dye dilution was used to assess the proliferative activity of lymphocytes; cell migration was studied with the Transwell system. The cytokine expression by activated macrophages was evaluated at the protein (ELISA) and RNA (reverse transcription and RT-PCR) levels.

Results. Elevated circulating Th17 level is associated with the severity of atherosclerosis in muscular (distal) but not elastic carotid artery segments (retrospective study, 70 patients). An imbalance between Treg and Th17 content with the predominance of proinflammatory Th17 is a risk factor

for progression of carotid atherosclerosis in patients with LDL levels below 3,5 mM (one-year prospective study, 33 patients, and 14 cases of progression). In patients with atherosclerosis, the number of circulating Tregs decreases with age; the number of effector T cells does not correlate with age (retrospective study, 111 patients). In patients with coronary atherosclerosis, the total number of circulating monocytes and the number of classical monocytes are lower, and the number of intermediate monocytes is higher. The content of classical monocytes is lower in patients with the most severe coronary atherosclerosis (retrospective study, 121 patients). Short-term high-dose therapy with atorvastatin is associated with a significant increase in Treg blood content and a decrease in CCR5 chemokine receptor expression by circulating monocytes (prospective study, 77 patients). Dose-dependent inhibition of migration and proliferation of CD4+ T-cells by statins, accompanied by an increase in the percentage of Foxp3+ cells, was found. Statins inhibit monocyte differentiation to Mph and cytokine synthesis by activated Mph at the posttranscriptional level. Cellular effects of "lipophilic" atorvastatin were manifested at lower concentrations compared to "hydrophilic" rosuvastatin.

Conclusion. The results of the study allow identifying patients prone to atherosclerosis progression; help to select drugs with an optimal combination of hypolipidemic, immunomodulatory, and anti-inflammatory activities, which is relevant for the treatment of patients with comorbidities, as well as to prevent complications.

049 EFFECTS OF AEROBIC PHISICAL

REHABILITATION ON MUSCLE TISSUE METABOLISM IN SEVERE HEART FAILURE PATIENTS

Galenko V.L.

Almazov National Medical Research Center, Saint-Petersburg, Russia

Aim. To evaluate efficiency and safety of aerobic physical rehabilitation (PR), based on original method; to study morphometric and metabolic changes in skeletal muscle fiber (MF) after PR.

Material and methods. 100 patients; heart failure (HF) with reduced ejection fraction (HFrEF), NYHA III, mean age 52±5,2 years, ejection fraction (EF) 27,3±4,2%, BMI 23,5±2,8 kg/m2. Before inclusion in PR program cardiopulmonary exercising test (CPET), echocardiography (EchoCG), quality of life (QOL), exercise tolerance (ET) were estimated. Physical training intensity was selected on the basis of lactate threshold (LT) achievement during CPET. PR efficiency was estimated on the basis of peak oxygen uptake (VO2peak), EF, QOL and ET dynamics after 6 months PR. Shin muscle biopsy was performed at baseline and after 3-6 months PR. In muscle samples activity of alkaline phosphatase (AP), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDG) were evaluated with plag-method. Data were statistically processed using software package "Statistika, 9.0".

Results. After 6 months of training EF increased by 10,5±2,3%, ET increased by 9,7±0,5 points (pij2<0,05), QOL changed by 24,8±3,5 points (significant regression of symptoms), VO2peak increased by 5,2±0,5 ml/min/kg (p34<0,05). MF diameter (dMF) after PR slightly decreased in 6 patients, in 2 patients it did not change. After 3-6 months of training AP activity increased by 24,2% (p<0,05); LDH activity in glycolytic MF decreased by 24,4%, in oxidative MF it decreased by 6,0% only (pj<0,05, p2>0,05). SDG activity in glycolytic MF increased by 20%, in oxidative MF it increased by 30% (pi<0,05, p2<0,05). There was a positive relationship between heart failure functional class dynamics and dMF (r=0,4, p=0,05), increase in CPET parameters was associated with AP activity (r=0,5, p=0,05).

Conclusion. 1. Aerobic physical rehabilitation in stable HF pts, selected on the basis of LT achievement, was effective in improving values of EF, QOL, VO2peak and ET. After 3-6 months PR dMF slightly decreased; 2. Participating in the PR program decreased LDH activity in both oxidative and glycolytic muscle fibers; it also increased AP and SDG activity significantly.

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Российский кардиологический журнал. 2021;26(S7), дополнительный выпуск (июнь)

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