Pathophysiology Of Atherosclerosis Research Articles

Thrombin generation and endothelial progenitor cell function among patients with acute myocardial infarction treated with prasugrel versus ticagrelor

Abstract Objectives To compare the effects of prasugrel and ticagrelor on thrombin generation (TG) and circulating endothelial progenitor cells (EPCs) in the acute phase of ST-segment elevation myocardial infarction (STEMI). Background TG, platelet function and EPCs have an important role in the pathophysiology of coronary artery disease (CAD). To date, the effect of novel P2Y12 inhibitors on these coagulation mediators has only been studied in the sub-acute phase following acute myocardial infarction. Methods Patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either ticagrelor or prasugrel treatment. TG, platelet reactivity and EPC were tested prior to P2Y12 inhibitor loading dose (T0), and 24 hours following PPCI (T1). Results Between December 2018 and July 2021, 83 consecutive STEMI patients were randomized to ticagrelor (N=42) or prasugrel (N=41) treatment. No differences were observed at T0 for all measurements. At T1, prasugrel was found to be a more potent TG inhibitor: lower thrombin peak levels (319.5±237.7 nmol/L vs. 433.5±264.3 nmol/L, p=0.06), longer time to peak (14.1±12.6 min vs. 8.3±9.7 min, p=0.03), longer lag time to TG initiation (7.7±7.5 min vs. 3.9±2.1 min, p<0.01) and a smaller AUC (2186.1±1123.1 vs. 3362.5±2108.5, p<0.01). Furthermore, levels of CD34 (2.6±4.1 vs. 1.1±1.1, p=0.01), CD133 (2.3±1.8 vs. 1.4±1.5, p=0.01) and CFUs (2.1±1.5 vs. 1.1±1.0, p<0.01) were significantly higher in the prasugrel group, as compared to the ticagrelor group. Conclusion Among STEMI patients treated with PPCI, treatment with prasugrel as compared to ticagrelor was associated with more potent inhibition of TG and improved EPCs count and function. Funding Acknowledgement Type of funding sources: None.

Gradually increased stress levels in the days leading to an acute myocardial infarction, detected by a new biomarker-based approach

Abstract Background Stress has been recognized as a cardiovascular risk factor that aside from triggering acute coronary syndromes (acute stress), could also directly and indirectly mediate the pathophysiology of coronary artery disease (chronic stress). So far, there have been no quantitative indices available to study this relationship. Purpose We prospectively investigated stress levels for the days prior to the episode, on male patients with an acute myocardial infarction (AMI), by measuring the Hair Cortisol Concentration (HCC) which is indicative of cortisol blood levels. Methods A total of 95 consecutive male patients with AMI (ST-elevation MI and non-ST-elevation MI) wererecruited. Exclusion criteria were: age >80 years, presence of chronic inflammatory disease, endocrine/psychiatric disorder or malignancy. A small sample of hair was obtained from the patient's head and the hair segments were later analyzed for HCC, by an enzymatic analytical method that measures the amount of cumulative cortisol which was deposited from the bloodstream upon every piece, at the time when it was generated by the hair follicle. Results Results of mean HCC of patients, expressed as a percentage of the range detected were: 0 time: 75.41%, 15 days prior: 76.79%, 30 days prior: 72.88%, 45 days prior: 69.34%, 60 days prior: 69.43% and 75 days prior: 65.96%. Figure 1 shows HCC during 75 days prior to the day of AMI occurrence which is the day zero. The results are consistent with a gradual increase in HCC, which reflects stress levels, in the days before the AMI, which peaked 15 days before the episode. Conclusions Stress levels, as quantified by a new biomarker-based approach, are gradually increased in the days preceding an AMI, peaking at 15 days before the episode. Funding Acknowledgement Type of funding sources: None.

Differences in microRNA expression in pericoronary tissue adjacent to atherosclerotic plaque and from lesion-free coronary artery

Abstract Background Pericoronary adipose tissue (PCAT) plays a key role in the pathogenesis of atherosclerosis. PCAT is a source of microRNAs (miRs) that acts as messengers for intercellular communication. In this study, we investigated whether the PCAT surrounding coronary occlusive atherosclerotic lesions shows specific miR expression patterns compared to PCAT surrounding plaque-free segments. Purpose To evaluate the expression of miRs that are known to be implicated in the pathophysiology of atherosclerosis. Methods We included 49 patients (38 men, age 65±9 years) with 3-vessel coronary artery disease, who underwent elective coronary bypass surgery. The PCAT was harvested from two sites: adjacent to an occlusive atherosclerotic coronary lesion, and a plaque-free segment. miR-133a, miR-21, miR-26b, miR-9 and miR-143 levels in PCAT cells were quantified by real-time reverse transcription polymerase chain reaction. Results miR-26b, miR-21 and miR-143 showed significantly greater expression in PCAT samples taken from around atheromatous plaque (154±295 versus 37±96, p=0.014, for miR-26b; 122±265 versus 29±79, p=0.014, for miR-21; and 181±356 versus 31±50, p=0.03, for miR-143) (Figure 1). In addition, the expression of miR-143, miR-26b and miR-21 in PCAT from atherosclerotic plaque showed robust positive correlations with body.mass index (r=0.451, p=0.001, r=0.41, p=0.03 and r=0.416, p=0.003 respectively), Conclusions Analysis of PCAT located in proximity to atherosclerotic plaque showed a different pattern of miR expression compared to PCAT in a plaque-free segment. Our findings open new perspectives for the role of PCAT in the pathophysiological mechanisms of atherosclerotic disease and should be further investigated. Funding Acknowledgement Type of funding sources: None.

Noninvasive diagnostic modalities for the diagnosis of coronary artery disease: A guide for acute care NPs.

Selecting noninvasive diagnostic tests for coronary artery disease can be a daunting task to acute care NPs. This article provides an overview of the pathophysiology of coronary artery disease, relevant noninvasive diagnostic imaging modalities, and an evidence-based approach to guide subsequent diagnostic and therapeutic interventions.

Hsa_circ_0007478 aggravates NLRP3 inflammasome activation and lipid metabolism imbalance in ox-LDL-stimulated macrophage via miR-765/EFNA3 axis

Coronary heart disease can be effectively prevented by alleviating atherosclerotic plaque progression. Ox-LDL-induced inflammatory response in macrophages is a critical factor in the pathophysiology of atherosclerosis. It is well known that circular RNAs (circRNAs) are associated with the progression of several human diseases, such as coronary artery diseases, by sponging microRNAs (miRNAs), but the function and hidden mechanisms of circRNAs in macrophage inflammation and lipid metabolism remain unclear. In our study, we established an ox-LDL-stimulated macrophage model and used microarray to detect circRNA expression in macrophages. The results revealed distinct profiles of circRNA expression across the ox-LDL-stimulated macrophage group and the control group. Among them, hsa_circ_0007478 was upregulated in ox-LDL-stimulated macrophages, accompanied by reduced miR-765 and increased EFNA3 expression. Activation of NLRP3 inflammasome and IL-1β in macrophages was decreased following silencing of hsa_circ_0007478 or transfection of miR-765 mimics. In addition, we demonstrated that as a direct target gene of miR-765, the expression of EFNA3 regulated NLRP3 inflammasome and IL-1β levels in macrophages. Besides, hsa_circ_0007478 promoted EFNA3 expression by acting as a miR-765 sponge. We further showed that hsa_circ_0007478/miR-765/EFNA3 axis could also be involved in the inhibition of the lipid metabolism and foam cells formation in ox-LDL-macrophages. Taken together, these findings suggest that Hsa_circ_0007478 may be a potential molecular target against the inflammatory response and foam cells during atherosclerosis.

Roles of Oxidative Stress and Inflammation in Vascular Endothelial Dysfunction-Related Disease.

Oxidative stress and chronic inflammation play an important role in the pathogenesis of atherosclerosis. Atherosclerosis develops as the first step of vascular endothelial dysfunction induced by complex molecular mechanisms. Vascular endothelial dysfunction leads to oxidative stress and inflammation of vessel walls, which in turn enhances vascular endothelial dysfunction. Vascular endothelial dysfunction and vascular wall oxidative stress and chronic inflammation make a vicious cycle that leads to the development of atherosclerosis. Simultaneously capturing and accurately evaluating the association of vascular endothelial function with oxidative stress and inflammation would be useful for elucidating the pathophysiology of atherosclerosis, determining treatment efficacy, and predicting future cardiovascular complications. Intervention in both areas is expected to inhibit the progression of atherosclerosis and prevent cardiovascular complications.

THE COMPLEX RELATIONSHIP OF PARAOXONASE GENE POLYMORPHISMS WITH CORONARY ARTERY DISEASE AND LIPID METABOLISM

Cardiovascular disorder (CVD) is one of the major reasons for mortality in developing and developed countries. According to the World Health Organization (WHO), non-communicable diseases (NCDs) are responsible for 50% of the overall disease burden in Pakistan. And among the NCDs, the most prevalent disease is CVD, as approximately every 1 out of 4 adults suffered from coronary artery disease (CAD). Coronary artery disease mainly causes ischemia or hypoxia of the heart due to coronary vessels stenosis or atherosclerosis.1 The key risk factors include smoking, dyslipidemia, hypertension, obesity, family history, and type 2 diabetes mellitus. The genetic contribution to CAD is an independent factor that includes genetic polymorphisms such as single nucleotide polymorphisms (SNPs). Genome-wide association studies (GWAS) suggest many genes SNPs involved in the pathogenesis of coronary artery disease.2 Although many studies identified the genes and single nucleotide polymorphisms but still, the role of these genetic factors is not clearly understood. Paraoxonase (PON) gene cluster is one of the most widely studied genes that consist of three genes PON1, PON2, and PON3, and located on chromosome 7. The PON2 is the oldest gene among this cluster however, all the 3 genes have a high structural homology. The International Union of Biochemistry and Molecular Biology classified the paraoxonases as aryldialkyl phosphatases. The enzymes coded by these gene clusters exhibit the antiatherosclerotic properties that play an essential role in high-density lipoproteins (HDL) or antioxidant properties. The PON1 activity is highly influenced by both genetic (non-modifiable) and environmental factors (modifiable).3 It involves a complex interaction between both genetic and modifiable factors. The human PON1 is a calcium-dependent glycoprotein that is first identified by its ability to hydrolyze various organophosphates. Through lipid peroxides hydrolysis, it reduces the low-density lipoprotein (LDL). Low enzyme levels are associated with cardiac disorders, familial hypercholesterolemia, and diabetes mellitus. To date, approximately 184 SNPs reported, and some coding region SNPs i.e. rs662 and rs854560 are the most widely studied single nucleotide polymorphisms.4 The most commonly studied Q192R polymorphism is associated with poor patient outcomes. The risk allele or R allele is associated with abnormal HDL and triglycerides levels and the worst CVD outcome. Furthermore, the levels of paraoxonase levels are also decreased in CVD patients and there is a complex relationship between different variables particularly genetic markers, lipid profile, or environmental factors with PON activity.5 The PON2 and PON3 similarly play a crucial role in lipid metabolism and inhibit atherosclerosis due to their protective role against the formation of atherosclerotic plaques in coronary arteries. In PON2 rs12704796 is significantly associated with coronary heart disease risk.6 Robertson et al. first reported single nucleotide polymorphism in PON3 at positions number 107 and 99 but the exact mechanism of these SNPs in the pathophysiology of CAD remains to be understood.7 The multi-locus model also revealed a gene to gene interaction between PON2 and PON3 and gene-environment in the Pakistani cardiac patients.8 The single nucleotide polymorphisms in this gene cluster are significantly important in CAD patients. These SNPs may exert their effect by modulating the lipid metabolism and enzyme concentrations in CAD patients, which can be varied according to certain environmental factors and ethnic groups. Thus, in the future, it is suggested to perform a study with more sample size in different populations that can help us in better understanding disease pathophysiology and prevention.

Neuregulin-1, a potential therapeutic target for cardiac repair.

NRG1 (Neuregulin-1) is an effective cardiomyocyte proliferator, secreted and released by endothelial vascular cells, and affects the cardiovascular system. It plays a major role in heart growth, proliferation, differentiation, apoptosis, and other cardiovascular processes. Numerous experiments have shown that NRG1 can repair the heart in the pathophysiology of atherosclerosis, myocardial infarction, ischemia reperfusion, heart failure, cardiomyopathy and other cardiovascular diseases. NRG1 can connect related signaling pathways through the NRG1/ErbB pathway, which form signal cascades to improve the myocardial microenvironment, such as regulating cardiac inflammation, oxidative stress, necrotic apoptosis. Here, we summarize recent research advances on the molecular mechanisms of NRG1, elucidate the contribution of NRG1 to cardiovascular disease, discuss therapeutic approaches targeting NRG1 associated with cardiovascular disease, and highlight areas for future research.

Epidemiology, Pathophysiology, and Management of Coronary Artery Disease in the Elderly.

Elderly patients over the age of ≥ 75 years are especially susceptible to coronary artery disease (CAD) as age is an important nonmodifiable risk factors for atherosclerosis and a predictor of poorer outcomes. In fact, CAD is a major cause of mortality and morbidity in this population. Due to concerns of functional frailty, comorbidities, and patient preference of conservative to no treatment have played a role in reducing the interest in pursuing prospective studies in this high-risk group. In this review, we provide an overview of the epidemiology, pathophysiology, and management of CAD in older adults.

Evaluation of the circulatory levels of resistin in coronary artery disease with associated co-morbidities

Inflammation is known to be the root cause of the development of coronary artery disease (CAD). Subclinical inflammation is one of the key players in pathophysiology of CAD. An inflammatory response leads to the secretion of various adipokines and cytokines. There are various pro-inflammatory markers which could be used to determine the onset of disease, and one such marker is resistin adipokine. The present study evaluates and compares the circulatory concentration of resistin in CAD patients and controls for the determination of its association with CAD. In this study, 58 CAD patients were enrolled and were further subdivided into four groups as per the associated co-morbidities. Various anthropometric and biochemical parameters were assessed. The circulatory levels of resistin were found to be significantly elevated in CAD patients and their subgroups as compared to controls. We conclude that elevated resistin levels in CAD patients suggest a key role of resistin in the development of CAD. The present study also observed that co-morbidities like type 2 diabetes can act as one of the major factors for the elevated concentration of resistin in the circulation of CAD patients with diabetes.

Intravascular molecular imaging: translating pathophysiology of atherosclerosis into human disease conditions.

Progression of atherosclerotic plaque in coronary arteries is characterized by complex cellular and non-cellular molecular interactions. Within recent years, atherosclerosis has been recognized as inflammation-driven disease condition, where progressive stages are characterized by morphological changes in plaque composition but also relevant molecular processes resulting in increased plaque vulnerability. While existing intravascular imaging modalities are able to resolve key morphological features during plaque progression, they lack capability to characterize the molecular profile of advanced atherosclerotic plaque. Because hybrid imaging modalities may provide incremental information related to plaque biology, they are expected to provide synergistic effects in detecting high risk patients and lesions. The aim of this article is to review existing literature on intravascular molecular imaging approaches, and to provide clinically oriented proposals of their application. In addition, we assembled an overview of future developments in this field geared towards detection of patients at risk for cardiovascular events.

Granzyme B+ CD4+ T cells associate with an unstable plaque phenotype in advanced human atherosclerosis

Background and Aims : Cytotoxic CD4+ T cells have previously been found in peripheral blood of patients with coronary artery disease1, however their occurrence in atherosclerotic plaques and their association with the pathophysiology of atherosclerosis has not been established.

Micrornas as potential novel biomarkers for vulnerable coronary plaque characteristics and exercise effects

Background and Aims : MicroRNAs (miRs) are negative regulators of protein synthesis in cells and are involved in the pathophysiology of atherosclerosis. Circulating miRs are therefore proposed as promising novel biomarkers of coronary artery disease (CAD). We hypothesized that circulating levels of miRs were associated with coronary plaque characteristics, plaque burden, and necrotic core volume, before and after aerobic exercise intervention.

Monocyte chemoattractant protein-1 serum levels in depending on history of percutaneous coronary intervention in patients with coronary artery disease with type 2 diabetes mellitus

Background and Aims : Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine, which plays a key role in the pathophysiology of both atherosclerosis and diabetes. MCP-1 is involved in the development of neoatherosclerosis after percutaneous coronary intervention (PCI). Investigate serum MCP-1 levels in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) depending on the previous history of PCI.

Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis.

BackgroundOsteoporosis and atherosclerosis are common in the elderly population, conferring a heavy worldwide burden. Evidence links osteoporosis and atherosclerosis but the exact underlying common mechanism of its occurrence is unclear. The purpose of this study is to further explore the molecular mechanism between osteoporosis and atherosclerosis through integrated bioinformatic analysis.MethodsThe microarray data of osteoporosis and atherosclerosis in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to identify the co-expression genes related to osteoporosis and atherosclerosis. In addition, the common gene targets of osteoporosis and atherosclerosis were analyzed and screened through three public databases (CTD, DISEASES, and GeneCards). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape. Then, the common microRNAs (miRNAs) in osteoporosis and atherosclerosis were screened out from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, the common miRNAs–genes network was constructed by Cytoscape software.ResultsThe results of common genes analysis showed that immune and inflammatory response may be a common feature in the pathophysiology of osteoporosis and atherosclerosis. Six hub genes (namely, COL1A1, IBSP, CTSD, RAC2, MAF, and THBS1) were obtained via taking interaction of different analysis results. The miRNAs–genes network showed that has-let-7g might play an important role in the common mechanisms between osteoporosis and atherosclerosis.ConclusionThis study provides new sights into shared molecular mechanisms between osteoporosis and atherosclerosis. These common pathways and hub genes may offer promising clues for further experimental studies.

Increased expression of miR-224-5p in circulating extracellular vesicles of patients with reduced coronary flow reserve

BackgroundEndothelial and microvascular dysfunction are pivotal causes of major adverse cardiac events predicted by coronary flow reserve (CFR). Extracellular Vesicles (EVs) have been studied extensively in the pathophysiology of coronary artery disease. However, little is known on the impact of the non-coding RNA content of EVs with respect to CFR.MethodsWe carried out a study among 120 patients divided by high-CFR and low-CFR to profile the miRNA content of circulating EVs.ResultsA multiplex array profiling on circulating EVs revealed mir-224-5p (p-value ≤ 0.000001) as the most differentially expressed miRNA in the Low-CFR group and showed a significantly independent relationship to CFR. Literature survey indicated the origin of the miR from liver cells and not of platelet, leukocyte, smooth muscle or endothelial (EC) origin. A q-PCR panel of the conventional cell type-EVs along with hepatic EVs showed that EVs from liver cells showed higher expression of the miR-224-5p. FACS analysis demonstrated the presence of liver-specific (ASGPR-1+/CD14−) EVs in the plasma of our cohort with the presence of Vanin-1 required to enter the EC barrier. Hepatic EVs with and without the miR-224-5p were introduced to ECs in-vitro, but with no difference in effect on ICAM-1 or eNOS expression. However, hepatic EVs elevated endothelial ICAM-1 levels per se independent of the miR-224-5p.ConclusionThis indicated a role of hepatic EVs identified by the miR-224-5p in endothelial dysfunction in patients with Low CFR.

Pathogenesis of Atherosclerosis: Review

In atherosclerosis, apolipoprotein B-lipoproteins in blood artery matrix attract monocytes, which become macrophages and dendritic cells. Macrophages generated from recruited monocytes cause a maladaptive, non-resolving inflammatory response that increases subendothelial layer. Some lesions cause myocardial infarction, stroke, and sudden cardiac death. Modern atherosclerosis research focuses on the molecular biology of atherogenesis, although the disease's complex pathophysiology is still unknown. The goal of this research is to examine the mechanisms of atherosclerosis development, such as endothelial dysfunction, fatty streak formation, fibrous plaque formation, and plaque rupture (Fig. 1.). This article takes a thorough look at the pathophysiology of atherosclerosis, addressing the pathological and biochemical mechanisms of atherosclerotic plaque development and growth. Atherosclerosis pathogenesis and disease development are the primary topics of discussion in this review, which focuses on the disease's particular targets.

Coronary artery lesion distribution in patients with chronic kidney disease undergoing percutaneous coronary intervention

Purpose To determine the location of coronary atherosclerosis distribution observed in patients with chronic kidney disease (CKD). Methods A cross-sectional study was conducted using the database of cardiovascular medicine data from Saitama Sekishinkai Hospital to clarify the association between renal function and angiographic characteristics of coronary atherosclerosis. In total, 3268 patients who underwent percutaneous coronary intervention were included. Propensity score matching revised the total to 1772. The association of renal function with the location and/or distribution of coronary atherosclerosis lesions was then examined. Results Overall, coronary lesion was observed in the left anterior descending coronary artery (LAD) in 56% patients, whereas 28% and 22% were in the right coronary artery (RCA) and left circumflex coronary artery (LCX), respectively. LAD was most affected and observed in 57% patients with stage 1 CKD. RCA was second-most affected, at 26% CKD stage 1, but it increased to 31%, 38%, and 59% in CKD 3, 4, and 5, respectively. In CKD 5 patients, the RCA was the most affected artery (59%), with 41% LAD lesions. Logistic regression analysis after propensity score matching showed that the odds ratios for an RCA lesion was 3.658 in CKD 5 (p = .025) compared with CKD 1 after adjusting for traditional risk factors. Conclusion The prevalence of RCA lesions, but not LAD or LCX lesions, increased with increasing CKD stage. The pathophysiology of coronary atherosclerosis may differ by lesion location. Deterioration of renal function may affect progression of atherosclerosis more in the RCA than in the LAD or LCX.

Novel Surrogate Markers of Cardiovascular Risk in the Setting of Autoimmune Rheumatic Diseases: Current Data and Implications for the Future.

Patients suffering from rheumatologic diseases are known to have an increased risk for cardiovascular disease (CVD). Although the pathological mechanisms behind this excess risk have been increasingly better understood, there still seems to be a general lack of consensus in early detection and treatment of endothelial dysfunction and CVD risk in patients suffering from rheumatologic diseases and in particular in those who haven't yet shown symptoms of CVD. Traditional CVD prediction scores, such as Systematic Coronary Risk Evaluation (SCORE), Framingham, or PROCAM Score have been proposed as valid assessment tools of CVD risk in the general population. However, these risk calculators developed for the general population do not factor in the effect of the inflammatory burden, as well as other factors that can increase CVD risk in patients with rheumatic diseases, such as glucocorticoid therapy, abnormal lipoprotein function, endothelial dysfunction or accelerated atherosclerosis. Thus, their sole use could lead to underestimation of CVD risk in patients with rheumatic diseases. Therefore, there is a need for new biomarkers which will allow a valid and early assessment of CVD risk. In recent years, different research groups, including ours, have examined the value of different CVD risk factors such as carotid sonography, carotid-femoral pulse wave velocity, flow-mediated arterial dilation and others in the assessment of CVD risk. Moreover, various novel CVD laboratory markers have been examined in the setting of autoimmune diseases, such as Paraoxonase activity, Endocan and Osteoprotegerin. Dyslipidemia in rheumatoid arthritis (RA) is for instance better quantified by lipoproteins and apolipoproteins than by cholesterol levels; screening as well as pre-emptive carotid sonography hold promise to identify patients earlier, when prophylaxis is more likely to be effective. The early detection of subtle changes indicating CVD in asymptomatic patients has been facilitated through improved imaging methods; the inclusion of artificial intelligence (AI) shows promising results in more recent studies. Even though the pathophysiology of coronary artery disease in patients with autoimmune rheumatic diseases has been examined in multiple studies, as we continuously gain an increased understanding of this comorbidity, particularly in subclinical cases we still seem to fail in the stratification of who really is at risk—and who is not. A the time being, a multipronged and personalized approach of screening patients for traditional CVD risk factors, integrating modern imaging and further CV diagnostic tools and optimizing treatment seems to be a solid approach. There is promising research on novel biomarkers, likewise, methods using artificial intelligence in imaging provide encouraging data indicating possibilities of risk stratification that might become gold standard in the near future. The present review concentrates on showcasing the newest findings concerning CVD risk in patients with rheumatologic diseases and aims to evaluate screening methods in order to optimize CVD risk evaluation and thus avoiding underdiagnosis and undertreatment, as well as highlighting which patient groups are most at risk.

Эффективность применения цилостазола у пациентов с перемежающейся хромотой

INTRODUCTION: Despite the intensive study of the pathophysiology, molecular and cellular mechanisms of atherosclerosis, the development and introduction of a number of new treatment methods, to date, the disease of the arteries of the lower extremities is one of the most pressing problems of modern vascular surgery and medicine in general. AIM: To evaluate the influence of cilostazol on the functional status of endothelium and pain-free walking distance in patients with lower limb artery diseases of atherosclerotic etiology. MATERIALS AND METHODS: The study was performed on 80 patients with obliterating atherosclerosis of lower limb arteries. Depending on the type of the given conservative therapy, the patients were divided to two groups. Group A (n = 40) included patients who received the baseline therapy in accordance with National recommendations on managing patients with peripheral artery diseases, and also medical drug Aducil® (cilostazol) 100 mg 1 tablet two times a day. Group В (n = 40) included patients who received only baseline therapy in accordance with National recommendations on managing patients with peripheral artery diseases. From all the patients, venous blood samples were taken for determining a number of markers of the endothelial dysfunction: endothelial nitric oxide synthase, prostacyclin, endothelin-1, interleukine-6. RESULTS: In 6 and 12 months after the start of the treatment, the level of endothelial nitric oxide synthase was reliably higher in group А patients (6 months — 12.91 (11.23–14.57) ng/ml; 12 months — 13.86 (12.42–16.25) ng/ml) in comparison with group В (6 months — 11.62 (8.63–16.73) ng/ml; 12 months — 11.76 (8.32–18.43) ng/ml) (р < 0.001). The level of prostacyclin was statistically significantly higher in group А after 6 months (group А — 18,532.88 (17,458.85–20,905.71) ng/ml; group В — 17,592.5 (15,542.56–19,721.52) ng/ml) and 12 months (group А — 18,452.27 (17,567.31–20,780.05) ng/ml; group В — 17,013.05 (15,090.1–19,517.58) ng/ml) in comparison with group В (р < 0.05). After 1 month from the start of treatment, the level of interleukin-6 was lower in group А (group А — 2.8 (2.23–3.4) ng/ml; group В — 3.65 (2.65–4.7) ng/ml), in 3 months — (group А — 2.4 (2–2.95) ng/ml; group В — 3.6 (2.55–4.5) ng/ml), 6 months (group А — 2.15 (1.73–2.88) ng/ml; group В — 3.45 (2.73–4.4) ng/ml), and 12 months (group А — 2.2 (1.93–2.95) ng/ml; group В — 3.3 (2.6–4.2) ng/ml) in comparison with group В (р < 0.001). No statistically significant difference in the levels of endothelin-1 was seen between group А and group В (p > 0.05). The analysis of the pain-free walking distance after 1 month (group А — 450 (436.25–487.5) m; group В — 250 (242.5–280) m), 3 months (group А — 455 (450–507.5) m; group В — 250 (250–277.5) m), 6 months (group А — 440 (430–487.5) m; group В — 235 (220–250) m), and 12 months (group А — 425 (410–465) m; group В — 210 (190–220) m) showed statistically reliable increase in the parameter in group А in comparison with group В (р < 0.001). Based on the results of USDS, the patients of group А showed statistically significant increase in the ankle-brachial index in 1, 3, 6 months (group А — 0.7 (0.7–0.7); group В — 0.6 (0.6–0.6)) and 12 months (group А — 0.7 (0.6–0.7); group В — 0.6 (0.5–0.6)) after the start of treatment in comparison with group В (р < 0.001). CONCLUSIONS: Treatment with cilostazol stimulates increase of the level of endothelial nitric oxide synthase and prostacyclin, and also promotes decrease in the level of interleukin-6. Cilostazol reliably increases pain-free walking distance and the ankle-brachial index.