Process Of Atherosclerosis Research Articles

The role of immunoglobins in atherosclerosis development; friends or foe?

Coronary artery disease, atherosclerosis, and its life-threatening sequels impose the hugest burden on the healthcare systems throughout the world. The intricate process of atherosclerosis is considered as an inflammatory-based disorder, and therefore, the components of the immune system are involved in different stages from formation of coronary plaques to its development. One of the major effectors in this way are the antibody producing entities, the B cells. These cells, which play a significant and unique role in responding to different stress, injuries, and infections, contribute differently to the development of atherosclerosis, either inhibitory or promoting, depending on the type of subsets. B cells implicate in both systemic and local immune responses of an atherosclerotic artery by cell-cell contact, cytokine production, and antigen presentation. In particular, natural antibodies bind to oxidized lipoproteins and cellular debris, which are abundant during plaque growth. Logically, any defects in B cells and consequent impairment in antibody production may greatly affect the shaping of the plaque and its clinical outcome. In this comprehensive review, we scrutinize the role of B cells and different classes of antibodies in atherosclerosis progression besides current novel B-cell-based therapeutic approaches that aim to resolve this affliction of mankind.

The Hypothesis of Trace Elements Involvement in the Coronary Arteries Atherosclerotic Plaques' Location.

Background: Coronary artery disease (CAD) is a chronic inflammatory disease with multiple well-known risk factors. Although epidemiological studies report improvements in classical CAD risk-factor control, except for diabetes and obesity, cardiovascular diseases remain the leading causes of morbidity and mortality in the current population. The question regarding the atherosclerotic plaque location in particular arteries remains unanswered. Research on novel possible aspects that could help to properly understand atherosclerosis pathophysiology is essential. This study was based on a body trace-elements analysis, measured in scalp hair samples, as possible co-factors of various enzymes that may be crucial for CAD development. Methods: A total of 133 consecutive male patients with a median age of 71 (65-75) years, who presented with anginal symptoms of CCS class 2.0 (0.3) without previous heart-related interventions, were included in the analysis. The results of the cine-angiography were compared with the demographical, clinical, and laboratory results, followed by scalp-hair trace analysis. The possible predictors for coronary disease locations in the left descending artery (LAD), the circumflex artery (Cx), and the right coronary artery (RCA) were the subjects of this study. Results: Statistically significant differences in the scalp-hair trace elements concentration between the CAD and normal angiogram groups were noticed for magnesium (p = 0.003), calcium (p < 0.001), chromium (p = 0.011), and copper (p = 0.043). The multivariable analysis for epicardial atherosclerotic disease revealed the co-existence of diabetes mellitus (OR: 2.94, 95% CI: 1.27-6.79, p = 0.012) as a possible causative factor for the LAD location. The multivariable analysis for the atherosclerosis location in the Cx artery presented scalp-hair magnesium as a possible predictive factor (OR: 0.98, 95% CI: 0.96-1.00, p = 0.024). The multivariable model for the RCA location of atherosclerotic plaque indicated scalp-hair Zn concentration (0.99, 95% CI: 0.98-1.00, p = 0.002) and serum HDL (OR: 0.61, 95% CI: 0.04-0.09, p = 0.016). Conclusions: Possible hypothetical distinctive pathomechanisms, in particular, coronary artery involvement, in atherosclerosis processes are presented in the male group. Diabetes mellitus was found to be the primary factor for left descending artery disease. The low scalp-hair magnesium concentration was found to be a possible risk factor involved in the circumflex artery atherosclerotic plaque location. The inverse relation between serum high-density lipoprotein, the scalp hair zinc concentration, and right coronary disease was noticed.

The role of integrin-related genes in atherosclerosis complicated by abdominal aortic aneurysm.

Increasingly, the shared risk factors and pathological processes of atherosclerosis and abdominal aortic aneurysm (AAA) are being recognized. The aim of our study was to identify the hub genes involved in the pathogenesis of atherosclerosis and AAA. The analysis was based on 2 gene expression profiles for atherosclerosis (GSE28829) and AAA (GSE7084), downloaded from the Gene Expression Omnibus database. Common differential genes were identified and an enrichment analysis of differential genes was conducted, with construction of protein-protein interaction networks, and identification of common hub genes, and predicted transcription factors. The analysis identified 133 differentially expressed genes (116 upregulated and 17 downregulated), with the enrichment analysis identifying a potential important role of integrins and chemokines in the common immune and inflammatory responses of atherosclerosis and AAA. Regulation of the complement and coagulation cascades and regulation of the actin cytoskeleton were associated with both diseases, with 10 important hub genes identified: TYROBP, PTPRC, integrin subunit beta 2, ITGAM, PLEK, cathepsin S, lymphocyte antigen 86, ITGAX, CCL4, and FCER1G. Findings identified a common pathogenetic pathway between atherosclerosis and AAA, with integrin-related genes playing a significant role. The common pathways and hub genes identified provide new insights into the shared mechanisms of these 2 diseases and can contribute to identifying new therapeutic targets and predicting the therapeutic effect of biological agents.

Alisol A inhibits and stabilizes atherosclerotic plaques by protecting vascular endothelial cells.

Dysfunction of endothelial cells represents a crucial aspect in the pathogenesis of atherosclerosis. The aim of this study was to explore the protective effects of alisol A on vascular endothelial cells and its possible mechanisms. An atherosclerosis model was established by feeding ApoE-/- mice with high-fat chow. Alisol A (150mg/kg/d) or atorvastatin (15mg/kg/d) was administered, and the levels of blood lipids were evaluated. The effect of the drugs on atherosclerotic plaques was observed by staining the aorta with Sudan IV. In vitro experiments were conducted using human aortic endothelial cells (HAECs) to assess the effects of alisol A on cell proliferation, migration, tubulation, secretion, and cellular integrity by CCK-8 assay, wound healing assay, angiogenesis assay, NO secretion, and release of LDH. Transcriptomics and molecular docking were used to explore the mechanism of plaque inhibition and stabilization by alisol A. Alisol A significantly reduced the aortic plaque area in ApoE-/- mice fed with high-fat chow. In vitro, alisol A had a protective effect on HAECs, which was reflected in the inhibition of vascular endothelial cell proliferation, promotion of NO secretion by vascular endothelial cells, inhibition of vascular endothelial cell migration and angiogenesis, and the maintenance of cell membrane integrity. Therefore, alisol A inhibited and stabilized atherosclerotic plaques and slowed down the process of atherosclerosis. Transcriptomics studies showed 4,086 differentially expressed genes (DEGs) in vascular endothelial cells after alisol A treatment. Enrichment analysis indicated that many genes involved in TNF signaling pathway were differentially expressed, and inflammatory genes were suppressed. The molecular docking results verified the hypothesis that alisol A has a low binding energy after docking with TNF target, and TNF could be a potential target of alisol A. Alisol A produced protection on vascular endothelial cells, achieving inhibition and stabilization of atherosclerotic plaques.

Algorithms for evaluation of minimal cut sets

Objective:We propose a way to enhance the evaluation of minimal cut sets (MCSs) in biological systems modeled by Petri nets, by providing criteria and methodology for determining their optimality in disabling specific processes without affecting critical system components. Methods:This study concerns Petri nets to model biological systems and utilizes two primary approaches for MCS evaluation. First is the analyzing impact on t-invariants to identify structural dependencies. Second is assessing the impact on potentially starved transitions caused by the inactivity of specific MCSs. This approach deal with net dynamics. These methodologies aim to offer practical tools for assessing the quality and effectiveness of MCSs. Results:The proposed methodologies were applied to two case studies. In the first case, a cholesterol metabolism network was analyzed to investigate how local inflammation and oxidative stress, in conjunction with cholesterol imbalances, influence the progression of atherosclerosis. The MCSs were ranked, with the top sets presented, focusing on those that disabled the fewest number of t-invariants. In the second case, a carbohydrate metabolism disorder model was examined to understand its impact on atherosclerosis progression. The analysis aimed to identify MCSs that could inhibit the atherosclerosis process by targeting specific transitions. Both studies utilized the Holmes software for calculations, demonstrating the effectiveness of the proposed evaluation methodologies in ranking MCSs for practical biological applications. Conclusion:The algorithms proposed in this paper offer an analytical approach for evaluating the quality of MCSs in biological systems. By providing criteria for MCS optimality, these approaches have potential to enhance the utility of MCS analysis in systems biology, aiding in the understanding and manipulation of complex biological networks.Algorithm are implemented within Holmes software, an open-source project available at https://github.com/bszawulak/HolmesPN.

Cardiovascular Risk in Patients with Ankylosing Spondylitis.

Objectives: Ankylosing spondylitis (AS) is an autoinflammatory, chronic disease. Patients with AS are at increased risk of cardiovascular disease (CVD). The link between AS and subclinical atherosclerosis is multifactorial and still not completely understood. The aim of this study was to examine the potential associations between carotid intima-media thickness (cIMT) and different cardiometabolic biomarkers in individuals with AS. Methods: A total of 96 patients with AS were prospectively included. cIMT was measured via ultrasonography. Multiple linear regression analysis was used to find the best predictors of cIMT values. Principal component analysis (PCA) was implemented to extract factors that were further tested via binary logistic regression analysis in relation to cIMT. Results: Waist circumference (WC), low-density lipoprotein cholesterol (LDL-c), and the BASDAI score were independently correlated with cIMT in AS patients (p = 0.037, p = 0.060, and p = 0.048, respectively; adjusted R2 = 0.113). PCA extracted four panels of biomarkers, i.e., "haematology-lipid-related factor" (i.e., ferritin, haemoglobin, HDL-c, and triglycerides), "proinflammatory-prothrombotic-related factor" (i.e., platelets, neutrophils, and C-reactive protein), "LDL-c-vitamin-related factor" (i.e., vitamins D and B12, and LDL-c), and "age-glucometabolic-related factor" (i.e., age and HbA1c), in relation to higher cIMT in patients with AS. Among these four clusters, "age-glucometabolic-related factor" was an independent predictor of increased cIMT (p < 0.001). Conclusions: In addition to traditional cardiometabolic risk factors, WC and LDL-c, the disease activity score (BASDAI) is independently related to subclinical atherosclerosis in AS patients. The joint involvement of heterogeneous cardiometabolic risk factors may reflect different pathophysiological processes of subclinical atherosclerosis in patients with AS.

Cortisol Stress Hormones as a Psychobiological Mechanism in Coronary Artery Disease: A Critical Review

Coronary artery disease (CAD) is the most common type of heart disease and affects the lives of 1 in 20 adults. CAD-associated healthcare costs are estimated to exceed $200 Billion annually in the United States alone. Psychosocial stress, mental distress, depression, and fatigue are all linked to CAD. While the underlying mechanisms are not fully understood, the involvement of cortisol in inflammation in the pathophysiological process in CAD has been demonstrated. The literature has documented some modifiable risk factors for CAD, such as diet and exercise; however, the scope of information on stress as a modifiable risk factor is limited. This critical review paper analyzed four empirical studies published between 2019 and 2023, all of which reviewed the role of cortisol stress hormones in CAD. The results of all four studies revealed that cortisol levels are associated with CAD, though the direction and magnitude of the relationship varied between studies. An overview of each study is provided, including a review of the methodology used, a summary of the main findings, and a discussion of limitations.

Spatial Transcriptomic Profiling of Human Saphenous Vein Exposed to Ex Vivo Arterial Haemodynamics-Implications for Coronary Artery Bypass Graft Patency and Vein Graft Disease.

Vein graft disease is the process by which saphenous vein grafts, utilised for revascularisation during coronary artery bypass graft surgery, undergo an inflammation-driven intimal hyperplasia and accelerated atherosclerosis process in subsequent years after implantation. The role of the arterial circulation, particularly the haemodynamic properties' impact on graft patency, have been investigated but have not to date been explored in depth at the transcriptomic level. We have undertaken the first-in-man spatial transcriptomic analysis of the long saphenous vein in response to ex vivo acute arterial haemodynamic stimulation, utilising a combination of a custom 3D-printed perfusion bioreactor and the 10X Genomics Visium Spatial Gene Expression technology. We identify a total of 413 significant genes (372 upregulated and 41 downregulated) differentially expressed in response to arterial haemodynamic conditions. These genes were associated with pathways including NFkB, TNF, MAPK, and PI3K/Akt, among others. These are established pathways involved in the initiation of an early pro-inflammatory response, leukocyte activation and adhesion signalling, tissue remodelling, and cellular differentiation. Utilising unsupervised clustering analysis, we have been able to classify subsets of the expression based on cell type and with spatial resolution. These findings allow for further characterisation of the early saphenous vein graft transcriptional landscape during the earliest stage of implantation that contributes to vein graft disease, in particular validation of pathways and druggable targets that could contribute towards the therapeutic inhibition of processes underpinning vein graft disease.

The Effect of Retinoids in Vascular Smooth Muscle Cells: From Phenotyping Switching to Proliferation and Migration.

Atherosclerosis, a term derived from the Greek "athero" (atheroma) and "sclerosis" (hardening), is a long-standing process that leads to the formation of atheromatous plaques in the arterial wall, contributing to the development of atherosclerotic cardiovascular disease. The proliferation and migration of vascular smooth muscle cells (VSMCs) and the switching of their phenotype play a crucial role in the whole process. Retinoic acid (RA), a natural derivative of vitamin A, has been used in the treatment of various inflammatory diseases and cell proliferation disorders. Numerous studies have demonstrated that RA has an important inhibitory effect on the proliferation, migration, and dedifferentiation of vascular smooth muscle cells, leading to a significant reduction in atherosclerotic lesions. In this review article, we explore the effects of RA on the pathogenesis of atherosclerosis, focusing on its regulatory action in VSMCs and its role in the phenotypic switching, proliferation, and migration of VSMCs. Despite the potential impact that RA may have on the process of atherosclerosis, further studies are required to examine its safety and efficacy in clinical practice.

Upaya Pencegahan Kejadian Hipertensi Melalui Edukasi Lansia di Kelurahan Sawah Padang Aua Kuning, Payakumbuh Selatan, Sumatera Barat

The elderly are the age group over 60 years. The elderly are at risk of various disease burdens such as diabetes mellitus, Alzheimer's, hypertension, and others. Hypertension is a condition characterized by an increase in blood pressure above 140/90 mmHg. Elderly people are at risk of developing hypertension due to the influence of age and the process of atherosclerosis. Many efforts can be made to prevent hypertension, namely maintaining a healthy diet, physical activity, and reducing stress. This effort can be carried out well if it is supported by ongoing education for the elderly regarding hypertension. This activity aims to provide education to the elderly to prevent hypertension and hopefully reduce the incidence of hypertension in the elderly. The method of this activity is carried out by providing education about hypertension and the efforts that need to be made to prevent hypertension to the elderly who attend Posyandu activities at the Sawah Padang Aua Kuning Subdistrict Health Center. The media used was hypertension education posters. After the counseling activity, a question and answer session was held regarding hypertension material. Many of the elderly asked questions and were enthusiastic about the material presented. It is hoped that in the future hypertension education can be carried out regularly to increase the knowledge of the elderly.

Chlorogenic acid attenuates idiopathic pulmonary fibrosis: An integrated analysis of network pharmacology, molecular docking, and experimental validation

AimsIdiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition, the cause of which remains unknown and for which no effective therapeutic treatment is currently available. Chlorogenic acid (CGA), a natural polyphenolic compound found in different plants and foods, has emerged as a promising agent due to its anti-inflammatory, antioxidant, and antifibrotic properties. However, the molecular mechanisms underlying the therapeutic effect of CGA in IPF remain unclear. The purpose of this study was to analyze the pharmacological impact and underlying mechanisms of CGA in IPF. Main methodsUsing network pharmacology analysis, genes associated with IPF and potential molecular targets of CGA were identified through specialized databases, and a protein-protein interaction (PPI) network was constructed. Molecular docking was performed to accurately select potential therapeutic targets. To investigate the effects of CGA on lung histology and key gene expression, a murine model of bleomycin-induced lung fibrosis was used. Key findingsNetwork pharmacology analysis identified 384 were overlapped between CGA and IPF. Key targets including AKT1, TP53, JUN, CASP3, BCL2, MMP9, NFKB1, EGFR, HIF1A, and IL1B were identified. Pathway analysis suggested the involvement of cancer, atherosclerosis, and inflammatory processes. Molecular docking confirmed the stable binding between CGA and targets. CGA regulated the expression mRNA of EGFR, MMP9, AKT1, BCL2 and IL1B and attenuated pulmonary fibrosis in the mouse model. SignificanceCGA is a promising multi-target therapeutic agent for IPF, which is supported by its efficacy in reducing fibrosis through the modulation of key pathways. This evidence provides a basis to further investigate CGA as an IPF potential treatment.

Effect of Arabica coffee and Robusta coffee on aortic tissue P selectin expression and plasma apolipoprotein A-1 (ApoA-1) levels in the early process of atherosclerosis

Effect of Arabica coffee and Robusta coffee on aortic tissue P selectin expression and plasma apolipoprotein A-1 (ApoA-1) levels in the early process of atherosclerosis

Role of ROS and autophagy in the pathological process of atherosclerosis.

Activation of autophagy and production of reactive oxygen species occur at various stages of atherosclerosis.To clarify the role and mechanism of autophagy and reactive oxygen species in atherosclerosis is of great significance to the prevention and treatment of atherosclerosis.Recent studies have shown that basal autophagy plays an important role in protecting cells from oxidative stress, reducing apoptosis and enhancing atherosclerotic plaque stability.Autophagy deficiency and excessive accumulation of reactive oxygen species can impair the function of endothelial cells, macrophages and smooth muscle cells, trigger autophagic cell death, and lead to instability and even rupture of plaques. However, the main signaling pathways regulating autophagy, the molecular mechanisms of autophagy and reactive oxygen species interaction, how they are initiated and distributed in plaques, and how they affect atherosclerosis progression, remain to be clarified.At present, there is no autophagy inducer used to treat atherosclerosis clinically.Therefore, it is urgent to clarify the mechanism of autophagy and find new targets for autophagy. Antioxidant agents generally have defects such as low reactive oxygen species scavenging efficiency and high cytotoxicity. Highly potent autophagy inducers and reactive oxygen species scavengers still need to be further developed and validated to provide more possibilities for innovative treatments for atherosclerosis.

Role of osteokines in atherosclerosis.

Despite their diverse physiologies and roles, the heart, skeletal muscles, and smooth muscles all derive from a common embryonic source as bones. Moreover, bone tissue, skeletal and smooth muscles, and the heart share conserved signaling pathways. The maintenance of skeletal health is precisely regulated by osteocytes, osteoblasts, and osteoclasts through coordinated secretion of bone-derived factors known as osteokines. Increasing evidence suggests the involvement of osteokines in regulating atherosclerotic vascular disease. Therefore, this review aims to examine the evidence for the role of osteokines in atherosclerosis development and progression comprehensively. Specifically discussed are extensively studied osteokines in atherosclerosis such as osteocalcin, osteopontin, osteoprotegerin, and fibroblast growth factor 23. Additionally, we highlighted the effects of exercise on modulating these key regulators derived from bone tissue metabolism. We believe that gaining an enhanced understanding of how osteocalcin contributes to the process of atherosclerosis will enable us to develop targeted and comprehensive therapeutic strategies against diseases associated with its progression.

ITIH4 reversed the effects of thrombin on VSMCs stiffness via JNK and ERK signaling pathway

Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. ERK inhibitor (PD98059) or JNK inhibitor (SP600125) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process.

The Interplay of Atherothrombotic Factors and the Evolving Landscape of Atherosclerotic Cardiovascular Disease: Comprehensive Insights from Recent Studies.

The aim of the current work is to present a thorough recapitulation of the emerging understanding of atherosclerotic cardiovascular disease and recommending avenues for future studies. Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality, influenced by a complex interplay of genetic, environmental, and atherothrombotic factors. Atherosclerosis, a multifaceted and dynamic process, is at the core of many CVDs. Recent studies have shed light on the multilayered nature of atherosclerosis and cardiovascular risk, emphasizing the need for a nuanced understanding of these diseases across different populations and disease mechanisms. This review synthesizes findings from 6 pivotal studies, shedding light on the intricate mechanisms underlying atherosclerotic cardiovascular events, the evolving understanding of atherosclerosis, and the potential pathways to attempt implementation in clinical practice. Insights into atherothrombotic factors, the role of macrophages, and the implications of aortic enlargement and coronary artery calcification underscore the complexity of CVD pathogenesis and highlight the need for comprehensive strategies in diagnosis, treatment, and prevention.

A Lipid-Structured Model of Atherosclerosis with Macrophage Proliferation

Atherosclerotic plaques are fatty deposits that form in the walls of major arteries and are one of the major causes of heart attacks and strokes. Macrophages are the main immune cells in plaques and macrophage dynamics influence whether plaques grow or regress. Macrophage proliferation is a key process in atherosclerosis, particularly in the development of mid-stage plaques, but very few mathematical models include proliferation. In this paper we reframe the lipid-structured model of Ford et al. (J Theor Biol 479:48–63, 2019. https://doi.org/10.1016/j.jtbi.2019.07.003) to account for macrophage proliferation. Proliferation is modelled as a non-local decrease in the lipid structural variable. Steady state analysis indicates that proliferation assists in reducing eventual necrotic core lipid content and spreads the lipid load of the macrophage population amongst the cells. The contribution of plaque macrophages from proliferation relative to recruitment from the bloodstream is also examined. The model suggests that a more proliferative plaque differs from an equivalent (defined as having the same lipid content and cell numbers) recruitment-dominant plaque in the way lipid is distributed amongst the macrophages. The macrophage lipid distribution of an equivalent proliferation-dominant plaque is less skewed and exhibits a local maximum near the endogenous lipid content.

Development and disease-specific regulation of RNA splicing in cardiovascular system.

Alternative splicing is a complex gene regulatory process that distinguishes itself from canonical splicing by rearranging the introns and exons of an immature pre-mRNA transcript. This process plays a vital role in enhancing transcriptomic and proteomic diversity from the genome. Alternative splicing has emerged as a pivotal mechanism governing complex biological processes during both heart development and the development of cardiovascular diseases. Multiple alternative splicing factors are involved in a synergistic or antagonistic manner in the regulation of important genes in relevant physiological processes. Notably, circular RNAs have only recently garnered attention for their tissue-specific expression patterns and regulatory functions. This resurgence of interest has prompted a reevaluation of the topic. Here, we provide an overview of our current understanding of alternative splicing mechanisms and the regulatory roles of alternative splicing factors in cardiovascular development and pathological process of different cardiovascular diseases, including cardiomyopathy, myocardial infarction, heart failure and atherosclerosis.

Progression in the Relationship between Exosome Production and Atherosclerosis.

Atherosclerosis (AS) is the leading cause of cardiovascular disease, causing a major burden on patients as well as families and society. Exosomes generally refer to various lipid bilayer microvesicles originating from different cells that deliver various bioactive molecules to the recipient cells, exerting biological effects in cellular communication and thereby changing the internal environment of the body. The mechanisms of correlation between exosomes and the disease process of atherosclerosis have been recently clarified. Exosomes are rich in nucleic acid molecules and proteins. For example, the exosome miRNAs reportedly play important roles in the progression of atherosclerotic diseases. In this review, we focus on the composition of exosomes, the mechanism of their biogenesis and release, and the commonly used methods for exosome extraction. By summarizing the latest research progress on exosomes and atherosclerosis, we can explore the advances in the roles of exosomes in atherosclerosis to provide new ideas and targets for atherosclerosis prevention, diagnosis, and treatment.

Assessment of the severity of associated ischemia in conditions of atherosclerosis of the carotid arteries and arteries of the lower extremities

The purpose of the research is to develop a method for assessing the severity of ischemic processes in multifocal atherosclerosis against the background of chronic cerebrovascular insufficiency and chronic ischemia of the lower extremities.Methods. The main methods used in this study are the methodology for the synthesis of hybrid fuzzy decision rules, exploratory analysis, and the Delphi expert assessment method; calculations were based on the G. Rush model and the E. Shortliff iterative model.Results. In the course of the research, particular decisive rules were synthesized to assess violations of the regulatory functions of the brain, ischemic disorders of the brain and lower extremities, disorders of the motor functions of the lower extremities, on the basis of which, using the iterative model of E. Shortliff and aggregating decisive rules, intermediate decisive rules were formed, which, in turn, entered the final decisive the rule "severity of ischemic interaction". Further, based on the final decisive rule, an algorithm was developed to assess the severity of ischemic interactions for comorbid patients with disintegration of affective-effector mechanisms of interaction between peripheral organs and regulatory functions of the central nervous system, allowing to assess the severity of the ischemic process and the risk of fatal complications in patients with the pathology in question.Conclusion. In the course of the conducted research, high results were demonstrated in the application of synthesized partial decision rules within the framework of the task set in this study, and the expediency of using the obtained models and methods in the practice of a neurologist, vascular surgeon, angioedrologist, neurosurgeon was also shown.