Chronic Endothelial Dysfunction Research Articles

Soluble urokinase plasminogen activator receptor (suPAR) in children with obesity or type 1 diabetes as a marker of endothelial dysfunction: a cross-sectional study.

Pediatric obesity and type 1 diabetes mellitus (T1DM) represent two common chronic diseases associated with chronic inflammation, endothelial dysfunction and long-term complications. The aim of the present study was to assess the possible diagnostic and prognostic value of soluble urokinase plasminogen activator receptor (suPAR), a marker of inflammation and impaired endothelial function, in children with the diseases.In this cross-sectional study, children and adolescents with T1DM (N = 41) or obesity (N = 37), aged < 18 years old, and without proteinuria were included, together with children of similar age and without evident morbidity that served as controls (N = 42). Serum samples were obtained during standard outpatient follow up and the urokinase-type plasminogen activator receptor (suPAR) concentrations were measured using a commercially available sandwich ELISA kit (DUP00, R&D systems). Clinical and biochemical indices that were also assessed include body mass index (BMI) z-score, Tanner stages, glycosylated haemoglobin (HbA1c), fasting lipid profile and serum creatinine. Mean serum suPAR levels were significantly higher in patients with obesity compared to patients with T1DM and controls, while children with T1DM had similar suPAR levels to controls. Also, serum suPAR levels showed a negative correlation with age (Spearman rho -0.359, p < 0.001) and serum creatinine levels (Spearman rho -0.334, p = 0.005), and a positive correlation with BMI z-score (Spearman rho 0.354, p = 0.009) in the whole cohort. Conclusion: Serum suPAR may be a useful predictive marker of inflammation or endothelial dysfunction for children with obesity and T1DM, as well as a promising therapeutic target. Further studies are needed in order to clarify whether the reported differences in suPAR levels could reflect a greater impairment of the inflammation status and endothelial function in children with obesity compared to children with T1DM. What is Known: • Paediatric obesity and type 1 diabetes are characterised by chronic inflammation and metabolic dysregulation. • Urokinase plasminogen activator receptor (uPAR) has been proposed as a useful biomarker for chronic inflammation and cardiovascular risk in adults. What is New: • Serum suPAR levels were increased in children and adolescents with obesity compared to those with T1DM and healthy controls; thus, obesity may affect the inflammatory status and endothelial function to a higher degree than T1DM during childhood. • Serum suPAR may serve as a diagnostic and predictive marker of inflammation and endothelial dysfunction for children and adolescents with obesity and T1DM.

Beyond Joints: Pulmonary Hypertension in Spondyloarthropathies (Literature review)

Spondyloarthritis (SpA) represents a complex and dynamic spectrum of inflammatory rheumatic diseases. A nuanced understanding of its clinical, genetic, and immunologic aspects is imperative for accurate diagnosis and effective management. The comprehensive literature review reveals a nuanced connection between spondyloarthropathies and pulmonary hypertension (PH), expanding our understanding of these conditions beyond joint pathology. The synthesis of data from various studies provides valuable insights into the complex interplay of factors contributing to the development of PH in individuals with SpA. The reviewed studies consistently indicate a heightened prevalence of elevated arterial blood pressure in the pulmonary artery among patients with ankylosing spondylitis and psoriatic arthritis. However, the limited research on reactive arthritis and other subtypes necessitates further exploration to determine the prevalence and characteristics of pulmonary hypertension across the entire spectrum of SpA. The identified gaps in research emphasize the importance of future studies that encompass the entire SpA spectrum, to provide a more complete understanding of the association with PH. It is crucial to consider all pathogenetic mechanisms, including the impact of chronic persistent inflammation, endothelial dysfunction, and other relevant factors. Recognizing the significance of these mechanisms is vital for comprehensive insights into the complex interplay between both pathologies, guiding the development of targeted interventions and enhancing patient care strategies. This discussion serves as a foundation for future research directions and clinical considerations in the evolving landscape of spondyloarthropathies. This comprehensive overview sets the stage for a deeper exploration of the intricate facets of SpA, including its systemic implications and emerging therapeutic strategies.

Early Detection of Atrial Fibrillation in Chronic Obstructive Pulmonary Disease Patients.

Atrial fibrillation (AF) is an important medical problem, as it significantly affects patients' quality of life and prognosis. AF often complicates the course of chronic obstructive pulmonary disease (COPD), a widespread disease with heavy economic and social burdens. A growing body of evidence suggests multiple links between COPD and AF. This review considers the common pathogenetic mechanisms (chronic hypoxia, persistent inflammation, endothelial dysfunction, and myocardial remodeling) of these diseases and describes the main risk factors for the development of AF in patients with COPD. The most effective models based on clinical, laboratory, and functional indices are also described, which enable the identification of patients suffering from COPD with a high risk of AF development. Thus, AF in COPD patients is a frequent problem, and the search for new tools to identify patients at a high risk of AF among COPD patients remains an urgent medical problem.

IL-33 supplementation improves uterine artery resistance and maternal hypertension in response to placental ischemia.

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 wk of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the Reduced Uterine Perfusion Pressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized that IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted intraperitoneal mini-osmotic pumps infusing recombinant rat IL-33 (1 µg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14 to 19. We found that IL-33 supplementation in RUPP rats reduces maternal blood pressure and improves the uterine artery resistance index (UARI). In addition to physiological improvements, we found decreased circulating and placental cytolytic Natural Killer cells (cNKs) and decreased circulating, placental, and renal TH17s in IL-33-treated RUPP rats. cNK cell cytotoxic activity also decreased in IL-33-supplemented RUPP rats. Furthermore, renal ROS and placental preproendothelin-1 (PPET-1) decreased in RUPP rats treated with IL-33. These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, renal ROS, and PPET-1 expression. These data suggest that IL-33 may have therapeutic potential in managing PE.NEW & NOTEWORTHY Though decreased IL-33 signaling has been clinically associated with PE, the mechanisms linking this signaling pathway to overall disease pathophysiology are not well understood. This study provides compelling evidence that mechanistically links reduced IL-33 with the inflammatory response and vascular dysfunction observed in response to placental ischemia, such as in PE. Data presented in this study submit the IL-33 signaling pathway as a possible therapeutic target for the treatment of PE.

Hyperuricemia is Equivalent to Type 2 Diabetes - Transforming Myth into Reality

Hyperuricemia is a metabolic disorder characterized by a high level of uric acid in the blood and was commonly thought to be associated with gout and nephrolithiasis. While hyperuricemia and T2D (Type 2 diabetes) are distinct medical conditions, they share certain similarities, and both have significant detrimental effects on humans. The prevalence of hyperuricemia and T2D has been alarmingly rising in the past two decades, and the development of these two conditions among young adults is worrisome for healthcare professionals. Research and debates have recently focused on a possible link between hyperuricemia and T2D. Individuals with persistent hyperuricemia are more likely to develop T2D. The underlying mechanisms contributing to these associations may involve chronic systemic inflammation, oxidative stress, and endothelial dysfunction. They are almost identical in etiology, pathophysiology, complications, and management. Recent studies have revealed an intricate relationship between these two conditions, suggesting hyperuricemia may be equivalent to T2D. Screening for hyperuricemia at an early stage can prevent the development of prediabetes and later overt T2D. This review article aims to explore the concept of hyperuricemia as an equivalent of T2D and shed light on the transforming perception of this association. Keywords: Uric acid, prehyperuricemia, hyperuricemia, type 2 diabetes, metabolic disorder, non-communicable disorder, endothelial dysfunction, systemic inflammation, oxidative stress, and preventive measures.

Navigating the Complexity: Updates in Diabetes-Related Cardiovascular Complications

The aim of this study is to offer a thorough examination of contemporary research concerning cardiovascular complications induced by diabetes, with a specific focus on coronary artery disease (CAD), diabetic heart attacks, diabetic peripheral artery disease (PAD), and diabetic hypertension. The period of analysis spans from 1988 to 2022, and the data utilized is extracted from secondary sources. Diabetes mellitus is a chronic metabolic disorder associated with an increased risk of cardiovascular complications, including coronary artery disease (CAD), heart attacks, strokes, peripheral artery disease (PAD), and hypertension. These complications are influenced by chronic hyperglycemia, insulin resistance, dyslipidemia, inflammation, and endothelial dysfunction. Diabetic-induced cardiovascular diseases significantly contribute to morbidity and mortality rates worldwide. The studies highlight the potential of plant-derived targeted therapies in reducing inflammation and endothelial dysfunction, providing promising avenues for improving patient outcomes. Additionally, research on diabetes-specific medications, imaging techniques, individualized glycemic targets, and combination therapies reveals new approaches to managing diabetic-induced cardiovascular diseases. Precision medicine, advancements in imaging, and lifestyle interventions offer valuable tools for personalized treatment plans and improved patient care. Public health initiatives that enhance diabetes management, raise awareness, and improve healthcare access are crucial for reducing the burden of cardiovascular complications in Nigeria and other regions affected by diabetes. Further research and collaboration among healthcare professionals will refine our understanding and enhance the management of diabetic-induced cardiovascular diseases, ultimately reducing their impact on individuals with diabetes.

Linking Malaria and Hypertension: Unveiling the Interconnected Pathophysiological Nexus

Malaria, a devastating infectious disease caused by Plasmodium parasites, has long been recognized for its direct impact on global health. Recent studies have unveiled a potential connection between malaria infection and the development of hypertension, a prevalent cardiovascular disorder worldwide. Understanding the underlying pathophysiological mechanisms linking these seemingly disparate conditions is crucial for comprehensive disease management and prevention. The pathogenesis of malaria involves complex interactions between the parasite and the host immune system, resulting in systemic inflammation, endothelial dysfunction, and organ damage. Chronic exposure to Plasmodium infection induces alterations in vascular function, hemodynamics, and immune responses, potentially contributing to the development of hypertension. Several proposed mechanisms underscore the link between malaria and hypertension, including chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulation of the renin-angiotensin-aldosterone system (RAAS). These mechanisms intertwine to disturb vascular homeostasis, leading to increased peripheral resistance and elevated blood pressure. Furthermore, the longterm consequences of repeated malaria episodes, especially in endemic regions, may potentiate vascular remodeling and contribute to the onset or exacerbation of hypertension in affected individuals. Genetic predispositions and environmental factors also play pivotal roles in modulating susceptibility to both malaria and hypertension. Recognition of this intricate association between malaria and hypertension prompts the necessity for integrated healthcare approaches encompassing effective malaria control strategies, early detection, and management of hypertension in endemic regions. Targeted interventions addressing common pathways, such as inflammation and endothelial dysfunction, may offer potential therapeutic avenues. Keywords: Malaria, Hypertension, Pathophysiology, Inflammation, Endothelial Dysfunction, Plasmodium Parasites, Cardiovascular Disorders, Immune Response, Vascular Remodeling, Global Health.

Viral infections in cardiometabolic risk and disease between old acquaintances and new enemies

Atherosclerosis is a chronic disease, characterized by chronic inflammation, endothelial dysfunction, and lipid deposition in the vessel. Although many major, well-identified risk factors for atherosclerosis [e.g., hyperlipidemia, hypertension, type 2 diabetes (T2D), smoking habit, and obesity] explain a lot about the risk, there is a considerable number of patients who develop atherosclerotic damage and undergo adverse events without presenting any of these established modifiable risk factors. This observation has stimulated an urgent need to expand knowledge towards the identification of additional, less established risk factors that may help in the assessment of risk and fill the gap of knowledge in the cardiovascular (CV) setting. Among them, the hypothesis of a possible relationship between viral infectious agents and atherosclerosis has risen since the early 1900s. However, there is still a great deal of debate regarding the onset and progression of CV disease in relation to the roles of the pathogens (as active inducers or bystanders), host genomic counterparts, and environmental triggers, affecting both virus abundance and the composition of viral communities. Accordingly, the aim of this review is to discuss the current state of knowledge on infectious agents in the atherosclerotic process, with particular focus on two environmental-related viruses, as examples of familiar (influenza) and unfamiliar [severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)] disease triggers.

Sexual Dysfunction in Female Patients with Type 2 Diabetes Mellitus—Sneak Peek on an Important Quality of Life Determinant

Type 2 diabetes mellitus (T2DM) is a multisystemic disease with a high global burden and chronic complications. Sexual dysfunction (SD) in patients with T2DM is an often-overlooked complication, despite its high impact on quality of life (QoL). Female sexual disorders can affect women of reproductive age as well as menopausal women. Proposed mechanisms are intertwining a variety of physiological, neurological, vascular, hormonal, and psychological variables. The impairment of sexual function has been linked to hyperglycemia, insulin resistance, chronic low-grade inflammation, endothelial dysfunction, neuropathy, and hormonal abnormalities. There are many different manifestations of female sexual dysfunction, such as insufficient sexual desire, diminished arousal, difficulty in eliciting orgasm, and pain during sexual engagement. Numerous studies have shown that the QoL of patients living with diabetes mellitus (DM) is lower than that of those without DM. SD in women with T2DM leads to deteriorated QoL. Treatment must be individualized based on the diagnosis and the sexual dysfunction as well as underlying medical, psychological, and interpersonal issues. The goal of modern medical care for patients living with diabetes is not to delay death but to improve their health and QoL. The present review article aimed to raise awareness about female sexual dysfunction in patients with T2DM and to provide an overview of its impact on QoL.

Mapping individual cardiac cell types and their contribution in the development of heart failure in a multiple comorbidity porcine model

Abstract Background Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired left ventricular (LV) relaxation and filling due to increased myocardial stiffness and hypertrophy. The development of HFpEF is associated with multiple, interrelated risk factors including obesity, chronic kidney disease (CKD), diabetes mellitus (DM), hypertension. Mechanistic studies have implied that comorbidity-driven chronic inflammation, oxidative stress, and endothelial dysfunction act as contributors to the onset and development of HFpEF. Multiple studies that support this HFpEF paradigm highlight the complexity of the disease with different pathways active in and across different cell types. A recently developed multiple comorbidity swine (MCS) model with DM, CKD hypercholesterolemia, demonstrate inflammation, microvascular endothelial dysfunction and LV diastolic dysfunction. This model mimics the slow progression of disease in patients and is therefore ideal to study the earliest mechanisms underlying HFpEF. Purpose Here we hypothesize that single nuclei RNA (snRNA) sequencing aid in mapping the contribution of each individual cardiac cell cluster to disease development, to improve our mechanistic understanding of HFpEF. Methods We performed snRNA sequencing to analyze the transcriptional landscape of the cardiac environment in the well validated MCS model. Frozen left ventricle myocardial samples of MCS (n=4) and healthy control (n=3) swine were used. Results The analysis included ∼100.000 individual nuclei and offers new insights in cell type specific mechanisms during HFpEF onset and development against the background of common comorbidities. We identified 34 different cell clusters, which together represent 6 major cell types. Besides cardiomyocytes (CMs), endothelial cells (ECs) and fibroblasts, a large population of immune cells and smaller populations of mural cells and neurons were present in both MCS and control swine. IPA pathway analysis predicts transcriptomic changes within the cell clusters in response to comorbidities including activation of semaphoring and estrogen signaling in the largest CM cluster (CM2) and activation of EIF2 signaling in ECs (Fig. 1). Gene set enrichment analysis confirmed the activation of HFpEF paradigm pathways in the MCS dataset. Overlap of human HFpEF heart bulk RNA sequencing data and the MCS dataset showed overlapping disease processes including interferon gamma (IFNG) signaling. Moreover, IFNG signaling and IFNG associated transcription factor STAT1 were activated in most of the CM and EC clusters. Conclusion These findings suggest an essential role of multiple pathways during the onset and development of HFpEF. Further improvement of our understanding of underlying molecular mechanisms and crosstalk between cell populations, could pinpoint drug targets and aid the development of new treatments for HFpEF.Top 5 IPA predicted canonical pathways

Immunological Reactivity and Intensity of Oxidative Stress in Stable Coronary Artery Disease

The aim. To analyze the relationship between immune response factors and the intensity of oxidation of lipoproteins and proteins in patients with stable coronary artery disease (CAD) to clarify the pathogenesis of coronary atherosclerosis.&#x0D; Materials and methods. A total of 179 patients with stable CAD of II-IV functional class, mean age 56 (49-62) years (main group) and 30 healthy individuals, mean age 49 (45-53) years (control group) were examined. The material for immunological research was peripheral venous blood. To determine the indicators of immunity, flow laser cytometry and enzyme-linked immunosorbent assay were used. Spectrophotometric and fluorometric methods were used to determine the levels of intermediate and final oxidation products of lipids and proteins, as well as antioxidant protection enzymes in the blood serum and in atherogenic lipoproteins.&#x0D; Results. A direct relationship between the activity of lipoprotein peroxidation and protein oxidation with a cell-type immune response and immune inflammation was revealed.&#x0D; Conclusions. The high intensity of lipid peroxidation and protein oxidation in patients with stable CAD (stable angina pectoris) is combined with significant activation of the T-cell component of the immune response (in terms of the ratio of helper and cytotoxic subpopulations of T-lymphocytes, high concentrations of pro-inflammatory cytokines, the state of the CD40/CD40L system, the level of expression of the CD95 apoptosis marker on cells), which indicates interdependence of T-cell immunity and oxidative stress in the pathogenesis of atherosclerosis. The dependence of the hyperproduction of pro-inflammatory cytokines by mononuclear blood cells on free radical oxidation of proteins, peroxidation of apoB proteins and the intensity of antiperoxide protection (catalase and superoxide dismutase enzymes) in patients with stable CAD indicates a contribution to the presence of oxidative stress and the development of immune inflammation. A comprehensive study of the factors of immunological reactivity, the violation of which can lead to the development of immunopathological reactions, and the intensity of oxidation of lipoproteins and proteins in patients with stable CAD helps to clarify the pathogenetic relationship between chronic immune inflammation, endothelial dysfunction and oxidative stress, and also substantiates the expediency of general therapeutic approaches to the treatment of CAD.

Abstract 022: Il-33 Supplementation Improves Vascular Function And Maternal Hypertension In Response To Placental Ischemia

Preeclampsia (PE), a leading cause of maternal/fetal morbidity and mortality, is a hypertensive pregnancy disorder with end-organ damage that manifests after 20 weeks of gestation. PE is characterized by chronic immune activation and endothelial dysfunction. Clinical studies report reduced IL-33 signaling in PE. We use the R educed U terine P erfusion P ressure (RUPP) rat model, which mimics many PE characteristics including reduced IL-33, to identify mechanisms mediating PE pathophysiology. We hypothesized IL-33 supplementation would improve blood pressure (BP), inflammation, and oxidative stress (ROS) during placental ischemia. We implanted i.p. mini-osmotic pumps infusing recombinant rat IL-33 (1 μg/kg/day) into normal pregnant (NP) and RUPP rats from gestation day 14-19. We assessed maternal BP, cytolytic NK (cNK) and T H 17 cells, cNK cell activity, ROS, preproendothelin-1 (PPET) expression, and uterine artery resistance index (UARI). MAP (mmHg) was 104±4 in NP vs 124±7 in RUPP (p&lt;0.05 vs NP) and lowered to 108±10 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Circulating cNKs (% gated) were 0.9±0.2% in NP vs 3.9±1.1% in RUPP (p&lt;0.05 vs NP) and decreased to 1.1±0.6% in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Circulating T H 17s (%CD4 + T cells) were 1.0±0.6% in NP vs 7.2±0.5% in RUPP (p&lt;0.05 vs NP) and 0.8±0.4% in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=8/group). Renal T H 17s, placenta cNKs and T H 17s followed similar trends. cNK cell activity (fold change) was 3.92±0.6 fold higher in RUPP vs NP (p&lt;0.05 vs NP) and decreased to -0.24±0.1 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=3/group). Renal ROS (relative light units/min/mg protein) was 452±33 in NP vs 676±44 in RUPP (p&lt;0.05) and decreased to 258±50 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=5/group). Placental PPET (fold change) was 2.36±0.4 fold higher in RUPP vs NP (p&lt;0.05) and decreased to 1.22±0.2 in RUPP+IL-33 (p=0.05 vs RUPP, n=6-7/group). UARI (arbitrary units) was 0.71±0.01 in RUPP vs 0.54±0.01 in NP (p&lt;0.05) and was lowered to 0.57±0.02 in RUPP+IL-33 (p&lt;0.05 vs RUPP, n=6/group). These findings demonstrate a role for IL-33 in controlling vascular function and maternal BP during pregnancy by decreasing inflammation, ROS, and PPET expression. These data suggest IL-33 may have therapeutic potential in managing PE.

МЕХАНИЗМЫ ТРОМБО-ВОСПАЛЕНИЯ У ПАЦИЕНТОВ С СИСТЕМНОЙ КРАСНОЙ ВОЛЧАНКОЙ

Introduction. Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease. According to different authors, the incidence of thrombotic complications in this disease is higher than the average in the population and can be up to 40%. Aim. The aim of the present review is to provide an overview of mechanisms of thrombosis in patients with systemic lupus erythematosus. Material and methods. Analytical review of foreign and native publications in PubMed and eLibrary.ru between 1985-2020. Results and discussion. SLE represents a model of inflammation-induced thrombosis. The hypercoagulability state which characterizes SLE seems to be associated with inflammation-driven alterations of the thrombotic balance. Tissue-nonspecific autoantibodies, as well as cytokines and acute phase proteins induce a proinflammatory endothelial cell phenotype. Platelets are activated following endothelial dysfunction; they participate in inflammatory and thrombotic events occurring in an injured area. One of the possible initiators of the thrombosis process is considered to be an interaction of antiphospholipid antibodies with phospholipids of platelet membranes, endothelium and phospholipid-linked plasma proteins. Local unbalanced thrombin generation leading to hypercoagulability is another source central for thrombosis. Patients with systemic lupus erythematosus show multidirectional disorders of the coagulation system, with predominance of hypercoagulation especially in patients with II-III degree of disease activity. Conclusion. The mechanism of thrombo-inflammation in systemic lupus erythematosus is multifactorial, involving all components of the hemostatic system. Chronic endothelial dysfunction, platelet activation, hypercoagulation, suppression of fibrinolysis reflects an interplay between thrombosis and inflammation. Persisting autoimmune inflammation plays a key role in these abnormalities.

Inflammatory and endothelial dysfunction markers in females with metabolic syndrome aged 50–75 years

Introduction: The prevalence of metabolic syndrome (MetS) in Indonesia is 39% and it is higher in females than in males (46% vs. 28%). Features of this syndrome comprise low-grade chronic inflammation and endothelial dysfunction from cardiometabolic abnormalities. High-sensitive C-reactive protein (HsCRP) is a biomarker of cardiovascular disease, whereas ferritin and pentraxin-3 (PTX-3) are markers of chronic inflammation. One of the markers of endothelial dysfunction is an intercellular cell adhesion molecule-1 (ICAM-1). Studies on MetS in women aged 50–70 years and using several markers of inflammation and endothelial dysfunction are rare. The study aimed to determine differences in HsCRP, ferritin, PTX-3, and ICAM-1 level between females with and without MetS aged 50–75 years. Methods: For this cross-sectional study, 160 females aged 50–75 years from South Jakarta were recruited, divided into MetS and non-MetS (control) groups, 80 participants each. Participants that met the inclusion criteria were assessed for vital signs and metabolic parameters (e.g., lipid profile, fasting blood glucose level, and waist circumference [WC]). The groups were compared using an independent t-test for inflammatory (i.e., HsCRP, PTX-3, and ferritin) and endothelial dysfunction (ICAM-1) (p &lt; 0.05) biomarkers. Results: The mean age of the MetS and control groups was 59.6 ± 5.6 and 59.2 ± 5.5 years. MetS criteria included WC of ≥80 cm (95.2%), increased blood pressure level (90.6%); and high-density lipoprotein cholesterol of &lt;50 mg/dL (76.2%). Significant differences were found between the MetS and control groups for ferritin (p = 0.027), PTX-3 (p = 0.045), and ICAM-1 (p = 0.004) but not for HsCRP (p = 0.136). Conclusion: Elevated ferritin, PTX-3 level, and ICAM-1 level are significantly associated with an increased Mets risk in females aged 50–75 years; however, the same is not true for HsCRP.

Gout and hyperuricaemia: modifiable cardiovascular risk factors?

Gout and hyperuricaemia are two clinical situations associated with an elevated risk of developing cardiovascular (heart failure, myocardial infarction, stroke) and metabolic and renal complications. One reason is probably related to the fact that the prevalence of hyperuricaemia and gout is high in clinical situations, which themselves involve a high cardiovascular risk, such as hypertension, diabetes, chronic kidney disease or obesity. However, recent studies suggest that hyperuricaemia may promote cardiovascular complications independently of other cardiovascular risk factors, by inducing chronic inflammation, oxidative stress, and endothelial dysfunction. The questions that arise today concern primarily the treatment of asymptomatic hyperuricaemia. Should it be treated to decrease the patients' cardiovascular risk and if so, starting from which level and towards which target? There are now several pieces of evidence indicating that this might be useful, but data from large studies are not unanimous. This review will discuss this issue as well as new well-tolerated treatments, such as febuxostat or SGLT2 inhibitors, which lower uric acid levels, prevent gout and lower the risk of cardio-renal events.

ANALYSIS OF COVID-19 IMPACT ON THE STATE OF HEALTH AND CARDIOVASCULAR FUNCTION OF CHILDREN 7-9 YEARS OLD

Influenza and acute respiratory viral infections pose significant challenges in paediatrics, given their high prevalence among children and the potential for severe and complicated cases, particularly in young age groups. Over the past 20 years, there have been three coronavirus epidemics that have caused a substantial number of severe cases, high mortality rates, and global transmission. This review aims to provide a comparative analysis of clinical and epidemiological features of coronavirus infections in children, drawing from the examples of SARS and MERS, and offers essential approaches and recommendations for the diagnosis and treatment of COVID-19. The review covers the etiology, epidemiology, laboratory diagnosis, clinical presentation, and treatment of severe acute respiratory syndrome. It also provides a brief historical overview of the epidemiology, diagnosis, and treatment of this disease. Unlike other respiratory viral infections, COVID-19 can result in persistent symptoms following the acute phase, known as post-infection COVID-19 syndrome, which can last for weeks or even months. The long-term effects of COVID-19 in children are not yet fully understood, and further research is needed to explore its true prevalence, pathogenesis, and lasting impacts. The management of paediatric post-infection COVID-19 syndrome requires a multidisciplinary approach, international collaboration, and consensus to ensure early detection and effective treatment in children.&#x0D; The article presents current scientific insights into the factors contributing to the development of a prolonged post-COVID period, including chronic systemic inflammation, endothelial dysfunction, coagulation disorders, autoimmune reactions, and other immunological changes. The COVID-19 outbreak serves as a reminder of the ongoing threat posed by infectious diseases caused by pathogenic viruses, highlighting the need for global cooperation and preparedness to effectively mitigate their spread.

Vessel-on-a-Chip: A Powerful Tool for Investigating Endothelial COVID-19 Fingerprints.

Coronavirus disease (COVID-19) causes various vascular and blood-related reactions, including exacerbated responses. The role of endothelial cells in this acute response is remarkable and may remain important beyond the acute phase. As we move into a post-COVID-19 era (where most people have been or will be infected by the SARS-CoV-2 virus), it is crucial to define the vascular consequences of COVID-19, including the long-term effects on the cardiovascular system. Research is needed to determine whether chronic endothelial dysfunction following COVID-19 could lead to an increased risk of cardiovascular and thrombotic events. Endothelial dysfunction could also serve as a diagnostic and therapeutic target for post-COVID-19. This review covers these topics and examines the potential of emerging vessel-on-a-chip technology to address these needs. Vessel-on-a-chip would allow for the study of COVID-19 pathophysiology in endothelial cells, including the analysis of SARS-CoV-2 interactions with endothelial function, leukocyte recruitment, and platelet activation. "Personalization" could be implemented in the models through induced pluripotent stem cells, patient-specific characteristics, or genetic modified cells. Adaptation for massive testing under standardized protocols is now possible, so the chips could be incorporated for the personalized follow-up of the disease or its sequalae (long COVID) and for the research of new drugs against COVID-19.

The Acute Effect of Trimethylamine-N-Oxide on Vascular Function, Oxidative Stress, and Inflammation in Rat Aortic Rings.

A growing body of evidence suggests that the gut microbiota affects the cardiovascular system directly and indirectly via biologically active molecules. TMAO, a key metabolite produced by gut bacteria is implicated in atherosclerosis and chronic endothelial dysfunction, but with an unclear effect on vascular tone, oxidative stress, and inflammation. Our study aimed to evaluate the acute effects of TMAO on vascular contractility in relation with oxidative stress markers and inflammation. Aortic rings were harvested from laboratory rats and placed in a tissue bath system containing TMAO in concentrations of 300, 100, 10µM, and control. Vascular tone under the influence of vasoconstrictor phenylephrine and non-endothelial-dependent vasodilator sodium nitroprusside was assessed using force transducers connected to a computer-based acquisition system. Oxidative stress and inflammation were quantified by vascular assessment of the activity of NF-κB, NRF2, SOD1, and iNOS by western-blotting and MDA by spectrofluorimetry. After the incubation of the aortic rings in TMAO solutions for 1h, there was no difference in vasoconstrictor and non-endothelial vasodilator response between the studied doses. TMAO acutely induced oxidative stress and inflammation, significantly increasing levels of MDA and the expression of NF-κB, NRF2, SOD1, and iNOS, mostly in a dose-dependent manner. Our study showed the lack of a short-term effect of studied TMAO doses on vascular contractility, but demonstrated an acute prooxidative effect and activation of major inflammatory pathways, which can partially explain the detrimental effects of TMAO in cardiovascular disease.

Cardiovascular Risk Factors, Angiographical Features and Short-Term Prognosis of Acute Coronary Syndrome in People Living with Human Immunodeficiency Virus: Results of a Retrospective Observational Multicentric Romanian Study.

People living with human immunodeficiency virus have increased cardiovascular risk due to a higher prevalence of traditional and particular risk factors such as chronic inflammation, immune dysregulation, endothelial dysfunction, coagulation abnormalities and antiretroviral therapy. In developed countries, coronary artery disease has become the most frequent cardiovascular disease and an important cause of mortality in these patients. The symptomatology of an acute coronary syndrome can be atypical, and the prevalence of each type of acute coronary syndrome is reported differently. Regarding coronary artery disease severity in people living with HIV, the literature data indicates that the presence of single-vessel disease is akin to that of HIV-negative patients, and their short-term prognosis is unclear. This study aims to assess the clinical characteristics, biological parameters, angiographical features and short-term prognosis of acute coronary syndrome in a cohort of Romanian people living with human immunodeficiency virus.

The acute effect of respiratory muscle training on microcirculation in patients with chronic heart failure

Background: Patients with chronic heart failure (CHF) present microcirculation alterations and vascular endothelial dysfunction. Exercise training programs have been shown to improve the functional status of these patients, however less is known yet about the acute systemic effect of exercise on peripheral muscle microcirculation. The aim of the present study was to investigate the acute effect of a respiratory muscle exercise bout on the microcirculation of non-exercising muscles (systemic effect). Materials and Methods: Thirty-four (30♂/4♀) stable CHF patients, with a mean age of61.4±9.2 years, ejection fraction (EF): 33.9±7.8%, maximal inspiratory pressure (MIP): 78.2±27.1 cmH2O, VO2max: 17.5±4.05 ml/kg/min, VE/VCO2 slope: 32.7±6.4 and a New York Heart Association classification (NYHA) ≥ ΙΙ participated in the study. Microcirculatory assessment was performed at rest and immediately after the respiratory exercise program (5 sets/10 repetitions, training load: 60% of MIP). Basal tissue oxygen saturation (StO2),oxygen consumption rate (OCR) and reperfusion rate (RR) were measured utilizing near-infrared spectroscopy(NIRS) at the thenar muscle along with the vascular occlusion test (VOT). Results: RR (%/min), following the release of vascular occlusion, as well as OCR (%/min) increased after the respiratory exercise program (from 3.4±1.6 to 3.9±1.7, p=0.007, and from 12.7±3.8 to 13.2±3.9, p=0.021 respectively), whereas the corresponding basal StO2values difference did not reach the level of statistical significance (from 85.5±6.4. to 84.7±6.2, p=0.065). Conclusions: In the present study, concerning patients with CHF, after an acute respiratory exercise bout, dynamic microcirculatory indices assessed by NIRS in peripheral, non-exercising muscles, were significantly altered.