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Introduction: Chronic inflammation is a major risk factor for coronary artery disease (CAD). Currently, the inflammatory cardiovascular risk is assessed via C-reactive protein (CRP) levels measured using a high-sensitivity assay (hsCRP). Monomeric CRP (mCRP) is a locally produced form of CRP that has emerged as a potential biomarker of inflammation., Aim: This study investigated whether mCRP levels are associated with premature CAD., Materials and Methods: This study comprised 103 participants of both sexes, including 50 patients 56 ± 7 years old with premature CAD and 53 patients 51 ± 10 years old without CAD. CAD was verified using coronary angiography, hsCRP levels were measured using a standard assay, and mCRP levels were measured using fluorescent cytometric beads conjugated with an anti-mCRP antibody., Results: The levels of hsCRP were 0.99 (0.59; 3.10) mg/L vs. 0.63 (0.35; 1.85) mg/L (p = 0.067), and mCRP 6.84 (4.20; 13.78) µg/L vs. 2.57 (0.32; 5.66) µg/L (p <0.001) in patients with CAD vs. patients without CAD, respectively. There was a weak positive correlation between the mCRP and hsCRP levels (ρ = 0.214; p = 0.030). hsCRP levels were below 2.0 mg/L (i.e., residual inflammatory cardiovascular risk should have been excluded) in 70% of patients with CAD and 79% of patients without CAD (p = 0.365). mCRP levels differed between the groups of patients with hsCRP levels below 2.0 mg/L: 5.14 (4.07; 10.68) µg/L vs. 2.77 (0.53; 5.00) µg/L in patients with or without CAD, respectively (p <0.001). Logistic regression analysis demonstrated that mCRP levels were independently associated with premature CAD. The adjusted odds ratio was 1.18 (95% CI 1.06-1.33, p = 0.004) per each µg/L increase in mCRP levels., Conclusion: Higher mCRP levels were associated with premature CAD, independent of hsCRP levels and traditional risk factors., Competing Interests: The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Melnikov, Kozlov, Okhota, Saburova, Avtaeva, Kuznetsova, Guria, Prokofieva, Riazantseva, Ji, Wu and Gabbasov.)

In this study, we investigated von Willebrand factor (VWF)-related parameters in 30 patients with stable coronary artery disease (CAD) and 50 patients without CAD. In both groups, the following were measured: the VWF antigen level (VWF:Ag); the VWF ristocetin cofactor activity (VWF:RCo); the VWF collagen-binding activity (VWF:CB); and VWF-mediated platelet adhesion. Platelet adhesion was measured in whole blood at a shear rate of 1300 s -1 using a microfluidic chamber with a collagen-coated surface. VWF:Ag and VWF:RCo were found to be the same in both groups of patients. However, VWF:CB was found to be lower in patients with CAD compared with patients without CAD, with values of 106.7% (82.1; 131.6) and 160.4% (112.5; 218.1), respectively ( p < 0.001). The decrease in platelet adhesion after GPIb inhibition was more pronounced in patients with CAD compared with patients of the control group, with recorded values of 76.0% (60.6; 82.1) and 29.3% (0.0; 60.4), respectively ( p < 0.001). After adjusting for traditional risk factors, the odds ratio for CAD was found to be 0.98 (95% CI, 0.97-0.99; p = 0.011) per 1% increase in VWF:CB activity, and 1.06 (95% CI, 1.03-1.09; p < 0.001) per 1% decrease in GPIb-mediated platelet adhesion. The findings presented in this paper indicate a possible critical role played by complex VWF-collagen-platelet interactions in the development of CAD.

This study investigated von Willebrand factor (VWF)-mediated platelet adhesion at high shear rates in patients with premature coronary artery disease (CAD). The study included 84 patients with stable premature CAD and 64 patients without CAD. Whole blood samples were perfused through a microfluidic cell over a collagen-coated surface at a shear rate of 1300 s -1 . Measurements were performed before and after the inhibition of VWF-specific platelet GPIb receptors with an anti-GPIb monoclonal antibody (mAb). Platelet adhesion decreased by 77.0% (55.9; 84.7) in patients with premature CAD and by 29.6% (0.0; 59.7) in control patients after the inhibition of VWF-platelet interaction with anti-GPIb mAb ( p < 0.001). After adjusting for traditional risk factors, the odds ratio for premature CAD per 1% decrease in GPIb-mediated platelet adhesion was 1.03 (95% CI, 1.02-1.05; p < 0.001). The optimal cut-off level value of GPIb-mediated platelet adhesion was 62.8%, with 70.2% sensitivity and 81.2% specificity for CAD. The plasma levels of VWF or antiplatelet therapy did not affect the GPIb-mediated component of platelet adhesion. Thus, the GPIb-mediated component of platelet adhesion was more pronounced in patients with premature CAD. This may indicate the possible role of excessive VWF-platelet interactions in the development of premature CAD.

This review aimed to trace the inflammatory pathway from the NLRP3 inflammasome to monomeric C-reactive protein (mCRP) in atherosclerotic cardiovascular disease. CRP is the final product of the interleukin (IL)-1β/IL-6/CRP axis. Its monomeric form can be produced at sites of local inflammation through the dissociation of pentameric CRP and, to some extent, local synthesis. mCRP has a distinct proinflammatory profile. In vitro and animal-model studies have suggested a role for mCRP in: platelet activation, adhesion, and aggregation; endothelial activation; leukocyte recruitment and polarization; foam-cell formation; and neovascularization. mCRP has been shown to deposit in atherosclerotic plaques and damaged tissues. In recent years, the first published papers have reported the development and application of mCRP assays. Principally, these studies demonstrated the feasibility of measuring mCRP levels. With recent advances in detection techniques and the introduction of first assays, mCRP-level measurement should become more accessible and widely used. To date, anti-inflammatory therapy in atherosclerosis has targeted the NLRP3 inflammasome and upstream links of the IL-1β/IL-6/CRP axis. Large clinical trials have provided sufficient evidence to support this strategy. However, few compounds target CRP. Studies on these agents are limited to animal models or small clinical trials.

The high-sensitivity C-reactive protein (hsCRP) assay measures the level of the pentameric form of CRP in blood. Currently, there are no available assays measuring the level of the monomeric form of CRP (mCRP), produced at sites of local inflammation. We developed an assay measuring the mCRP level in blood plasma with functional beads for flow cytometry. The assay was used to measure the mCRP level in 80 middle-aged individuals with initially moderate cardiovascular SCORE risk. By the time of the mCRP measurement, the patients have been followed up for subclinical carotid atherosclerosis progression for 7 years. Ultrasound markers of subclinical atherosclerosis, which included plaque number (PN) and total plaque height (PH), were measured at baseline and at the 7th-year follow-up survey. Inflammatory biomarkers, including mCRP, hsCRP, inteleukin-6 (IL-6) and von Willebrand factor (VWF) level, were measured at the 7th-year follow-up survey. The median level of mCRP was 5.2 (3.3; 7.1) μg/L, hsCRP 1.05 (0.7; 2.1) mg/L, IL-6 0.0 (0.0; 2.8) pg/mL, VWF 106 (77; 151) IU/dL. In the patients with the mCRP level below median vs. the patients with the median mCRP level or higher, change from baseline in PN was 0.0 (0.0; 1.0) vs. 1.0 (1.0; 2.0) and PH 0.22 (-0.24; 1.91) mm vs. 1.97 (1.14; 3.14) mm, respectively ( p < 0.05). The adjusted odds ratio for the formation of new carotid atherosclerotic plaques was 4.7 (95% CI 1.7; 13.2) for the patients with the median mCRP level or higher. The higher mCRP level is associated with the more pronounced increase in PN and PH in patients with normal level of traditional inflammatory biomarkers and initially moderate cardiovascular SCORE risk., (Copyright © 2022 Melnikov, Kozlov, Pogorelova, Tripoten, Khamchieva, Saburova, Avtaeva, Zvereva, Matroze, Kuznetsova, Prokofieva, Balakhonova and Gabbasov.)

The aim of the study was to evaluate the levels of mediators of the immune response, cellular immunity, and phagocytic activity in patients with chickenpox with various values of the clinical and laboratory parameters and propose criteria for predicting the severity and complications of the disease., Materials and Methods: The blood levels of pro-inflammatory mediators were evaluated by ELISA using monoclonal antibodies (Protein Contour, Russia)., Results: The inflammatory mediators and neutrophil chemiluminescence were studied in patients with either presence or absence of Varicella zoster DNA. We found that in patients with positive viral DNA, the levels of IFN-α and IFN-γ were significantly lower compared to patients with negative DNA results. Thus, complications of chickenpox, in particular secondary viral-bacterial pneumonia, can be predicted based on low (less than double-normal) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. This type of immune response indicates the state of immune deficiency with prevailing suppression of the T-effector and phagocytic mechanisms in these patients., Conclusion: Prognosis of the development of severe and complicated forms of chickenpox can be based on the insufficiently increased (less than two normal values) levels of IL-6 and IFN-γ, induced chemiluminescence, CD16, and CD20. These relatively low levels are indicative of reduced immune response to the infection, which may require additional immune correcting therapy., Competing Interests: Conflict of interest. The authors declare no conflicts of interest to be reported.

The objective of this work was to study the ability of blood cells and their microparticles to transport monomeric and pentameric forms of C-reactive protein (mCRP and pCRP) in the blood of patients with coronary artery disease (CAD). Blood was obtained from 14 patients with CAD 46 ± 13 years old and 8 healthy volunteers 49 ± 13.6 years old. Blood cells and microparticles with mCRP and pCRP on their surface were detected by flow cytometry. Messenger RNA (mRNA) of CRP was extracted from peripheral blood monocytes stimulated with lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). mRNA of CRP in monocytes was detected with PCR. Monocytes were predominantly pCRP-positive (92.9 ± 6.8%). mCRP was present on 22.0 ± 9.6% of monocyte-derived exosomes. mCRP-positive leukocyte-derived microparticle counts were significantly higher (8764 ± 2876/µL) in the blood of patients with CAD than in healthy volunteers (1472 ± 307/µL). LPS and GM-CSF stimulated monocytes expressed CRP mRNA transcripts levels (0.79 ± 0.73-fold), slightly lower relative to unstimulated hepatocytes of the HepG2 cell line (1.0 ± 0.6-fold), but still detectable. The ability of monocytes to transport pCRP in blood flow, and monocyte-derived exosomes to transmit mCRP, may contribute to the maintenance of chronic inflammation in CAD., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The purpose of the study was to assess whether the occurrence of restenosis is associated with CD45+ platelet count and neutrophil to lymphocyte ratio in patients with type 2 diabetes mellitus (DM) after drug-eluting stent (DES) implantation for stable coronary artery disease (CAD). The study comprised 126 patients, including 55 patients with type 2 DM and stable CAD who underwent elective coronary artery stenting with DES and follow-up angiography within 6 to 12 months. Blood samples were collected from each patient on the morning of the coronary angiography procedure. The variables related to in-stent restenosis were selected by logistic regression analysis. The logistic regression analysis showed that 2 inflammatory factors, CD45+ platelet count (odds ratio [OR] = 4.51, 95% confidence interval [CI]: 1.50-13.50, P = .007) and neutrophil to lymphocyte ratio (OR = 3.09, 95% CI: 1.05-9.10, P = .04), were significantly associated with the risk of in-stent restenosis after stenting with DES in patients with stable CAD and type 2 DM. A receiver operator characteristic curve analysis indicated that the area under the curve was 0.83% (0.05%; P < .001), which showed that the logistic model had good predictive accuracy (based on CD45+ platelet count and neutrophil to lymphocyte ratio) for the risk of in-stent restenosis development in DES in patients with CAD and type 2 DM. Two novel biomarkers of restenosis, CD45+ platelet count and neutrophil to lymphocyte ratio, may be effectively used to predict in-stent restenosis after DES implantation in patients with CAD and type 2 DM.

The purpose of study is to investigate significance of detection of number of CD45-positive thrombocytes and ratio neutrophils/lymphocytes in evaluation of risk of development of re-stenosis after implantation of drug-eluting stents in patients with chronic ischemic heart disease and diabetes mellitus type II. The examination was applied to 126 patients with chronic forms of ischemic heart disease who passed through repeat coronary angiography during first year after implantation of drug-eluting stents. The patients were separated on two groups depending on availability of diabetes mellitus type II. In both groups, the patients passed through comparing of angiography and clinical characteristics. Also, a logistic model was developed prognosticating development of re-stenosis. The re-stenosis developed more often in patients with diabetes mellitus type II (54.5%) than in patients without diabetes mellitus type II (32.4%; p=0.01). The comparative analysis of more than 35 characteristics permitted to establish risk factors of development of re-stenosis with the highest prognosticating capacity among patients with diabetes mellitus type II. These risk factors were CD45-positive thrombocytes and ratio neutrophils/lymphocytes. To prognosticate development of re-stenosis a logistic regression model was developed comprising number of circulating CD45-positive thrombocytes, ratio neutrophils/lymphocytes and availability of diabetes mellitus type II. The model demonstrated high prognosticating value as regards development of re-stenosis: OR = 15.1 (95% CI 4.81-31, p < 0.001). The square under ROC-curve: AUC = 0.83 (95% CI 0,72-0,92; р < 0,001). The increasing of number of circulating CD45-positive thrombocytes and ratio neutrophils/lymphocytes can be considered as a valuable risk factors of development of re-stenosis in case of diabetes mellitus type II., Competing Interests: The authors declare no conflict of interest.

Objective: The aim of this study was to assess CD45-positive platelets (CD45+ platelets) involvement in restenosis development after drug-eluting stent (DES) implantation in patients with stable coronary artery disease (CAD)., Methods: The study comprised 126 male and female patients with stable angina pectoris, who underwent elective coronary stenting with DES and follow-up angiography within 6-12 months. The patients were assigned to the group with restenosis (n = 53) or group without restenosis (n = 73) according to the follow-up angiograms. In both groups we compared the level in blood of CD45+ platelets, the clinical, laboratory and angiographic variables, which may affect the development of restenosis. We have also constructed a logit regression model for prognosis of restenosis occurrence after DES implantation., Results: The blood count of CD45+ platelets was higher in patients with restenosis than in patients without: 0.82 % (0.58; 1.12) vs. 0.34 % (0.20; 0.68), p < 0.001, data are expressed as median (lower quartile; upper quartile). By binary comparisons of more than 35 different clinical, laboratory and angiographic variables we identified 8 significant risk factors for the development of stent restenosis after DES. In order to define the risk of the development of restenosis, we have built a logit regression model. The resulting logit regression equation included the level of CD45+ platelets, the neutrophil to lymphocyte ratio (NLR), small diameter arteries stenting and the number of simultaneously implanted stents in one patient. Receiver operating characteristic (ROC) curve analysis has demonstrated the high prognostic value of the resulting logit regression equation with an area under the curve (AUC) of 0.91 % (p < 0.001)., Conclusions: The acquired data indicate the presence of a close relationship between circulating CD45+ platelets and restenosis development after DES implantation in patients with stable CAD.

The purpose of research - the study of the level of soluble receptor for advanced glycation end products (CNG) in patients with coronary heart disease (CHD) with angina pectoris who have emerged restenosis after implantation of drug-eluting stents.

It has been found that in 15% of acute myocardial infarction patients' platelets generate reactive oxygen species that can be detected with luminol-enhanced chemiluminescence of platelet-rich plasma within 8-10 days after acute myocardial infarction. This increase in generate reactive oxygen species production coincides with the emergence of CD45(+) platelets. The ability of platelets to carry surface leukocyte antigen implies their participation in exchange of specific proteins in the course of acute myocardial infarction. Future studies of CD45(+) platelets in peripheral blood of acute myocardial infarction patients in association with generate reactive oxygen species production may provide a new insight into the complex mechanisms of cell-cell interactions associated with acute myocardial infarction.

Aim: To study the role of eosinophil granulocytes in the development of restenosis after drug-eluting stent (DES) implantation., Materials and Methods: The blood levels of eosinophils, eosinophil cationic protein (ECP), immunoglobulin E (IgE), and C-reactive protein (CRP) were compared in 170 patients with coronary heart disease (CHD) and stable angina who had undergone recoronarography within the first year after endovascular myocardial revascularization using DES. The blood level of eosinophils was determined by the results obtained employing the FACS Calibur flow cytofluorometer (Becton Dickinson, USA). That of ECP, IgE, and CRP was estimated by enzyme immunoassay by means of an Immulite-100 analyzer (Siemens, Germany). The data were presented as median (25th percentile and 75th percentile)., Results: The blood eosinophil level was 272 (234; 292) cells/μl in patients with restenosis while that was 134 (85; 156) cells/μl in those without restenosis (p = 0.002). The plasma ECP level proved to be greater in the patients who had developed restenosis after DES implantation than in those who had not [17.7 (11.2; 24) and 9 (6.4; 12.9) ng/ml, respectively (p = 0.017). At 6 months after DES implantation, the level of ECP was significantly higher (8.6 (7.3; 9.7) ng/ml) than the baseline level (p = 0.04). Later on, there was an even greater increase in ECP levels. No significant changes were noted in blood ECP levels after bare stent implantation., Conclusion: The findings suggest that there is a relationship between the occurrence of restenosis and the enhanced activity of eosinophil granulocytes in CHD patents after DES implantation.

Aim of the study was to assess activation of eosinophils as well as allergic and inflammatory reactions of the body in development of restenosis after implantation of stents with drug covering. We included into the study 32 patients with ischemic heart disease (IHD) and stable angina subjected to repeat coronary angiography during first year after endovascular myocardial revascularization with the help of stents with drug covering, and 11 healthy persons. Levels of eosinophilic cation protein (ECP), immunoglobulin E (IgE), and C-reactive protein (CRP) in blood plasma of patients and healthy persons was determined by immunoenzyme assay. According to results of angiographic study patients were divided into 2 groups: the first comprised 19 patients in whom no instent restenosis was found, the second comprised 13 patients in whom formation of restenosis at least in one stent was noted. Patients in these groups did not differ by age, sex, smokers and nonsmokers ratio, presence of hyperlipidemia, and angiographical characteristics of involved arteries. In patients with restenosis of stents blood plasma ECP level was 17.7 (11.2-24.0) g/ml and significantly higher than in patients without restenosis [9.0 (6.4-12.9) g/ml; p=0.017]. Blood level of IgE in these groups of patients did not differ [58.8 (42.1-164.0) and 52.9 (12.8-76.1) mg/ml, respectively; p=0.40] and did not differ from IgE level in blood of healthy volunteers [32.0 (21.2-80.8) mg/ml; p=0.91]. CRP level in patients with IHD was higher than in healthy volunteers [0.36 (0.1-0.75) mg/ml; p=0.0008)], but did not differ significantly in groups of patients with and without restenosis [2.38 (0.30-4.08) and 1.63 (0.61-2.47) mg/ml, respectively; p=0.52]. It was found that in the group of patients with low blood level of ECP (&lt;11 g/ml) restenoses were revealed in 19% while in the group with higher blood level of ECP (&gt;11 g/ml) - in 62% of cases (p=0,019). In patients subjected to coronary stenting with higher level of ECP in blood we noted more frequent development of restenoses than in patients with low level of this protein. The data obtained allow to suggest presence of relationship between development of restenosis and elevated activity of eosinophilic granulocytes in patients with IHD after revascularization.

Aim of the study was to assess participation in development of restenosis of circulating in blood progenitor cells of stromal line of differentiation and polymorphonuclear granulocytes. We compared levels of osteonectin positive progenitor cells, neutrophils, eosinophils, and basophils in blood of patients with ischemic heart disease (IHD) in whom according to data of angiographic study after endovascular myocardial revascularization with the help of stents with drug coating (Cypher, Cordis Corp, USA) restenosis was detected (n=15), in patients without restenosis (n=23), and in healthy persons (n=17). Levels of stromal progenitor cells and polymorphonuclear granulocytes in blood were measured with the help of methods of flow cytometry. In groups of patients with IHD with and without restenosis number of osteonectin positive cells in blood was higher than in healthy subjects (2.4+/-0.7 and 2.5+/-0.9 vs 1.5+/-0.5 cells/ microL, respectively, p=0.004) without significant differences between groups (p=0.59). These 2 groups of patients did not differ by numbers of leukocytes, neutrophils, and basophils in blood. At the same time we found that in patients with restenosis number of eosinophils in blood was significantly greater than in the group of patients without restenosis (262+/-68 vs 124+/-67 cells/ microL, respectively p<0.001). Moreover in patients with level of eosinophils exceeding 170 cells/ microL rate of development of restenosis was 74% against 5% in patients with number of eosinophils less than 170 cells/ microL (p<0.001). Thus level of stromal progenitor cells in blood of patients with IHD was higher than in healthy persons and remained equally high in groups with and without restenosis. Number of blood eosinophilic leukocytes in patients who had been subjected to coronary stenting in whom later restenosis developed was significantly higher than in patients without restenosis. The data obtained indicate at the presence of link between development of in - stent restenosis and elevated content of eosinophilic granulocytes in blood of patients with IHD.

Using plasminogen-Sepharose 4B chromatography, a 50-70% reduction in the alpha-2-antiplasmin (alpha-2-AP) content in human and dog blood plasma was reached. The decrease in the alpha-2-AP concentration in human and dog blood plasma markedly enhanced the lysis of fibrin clots formed from the plasma under the action of urokinase and streptokinase. Thus, the lysis of model clots for a definite period of time for human and dog blood plasma depleted for alpha-2-AP by 50-70% required 5-8 and 3-6 times as low urokinase and streptokinase concentrations as those needed for the clot lysis in the native plasma. The decrease in the fibrinogen concentration in human blood plasma caused by plasmosorption on plasminogen-Sepharose enhanced the model fibrin clot lysis by urokinase and streptokinase, however, by no more than 5-10%. Hence, the increased efficiency of plasminogen activators in the given model system can be accounted for by the decline of the antiplasmin potential of the blood plasma.