Risk Factor For Endothelial Dysfunction Research Articles

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

Association between Relative Thrombocytosis and Microalbuminuria in Adults with Mild Fasting Hyperglycemia.

An elevated platelet count may contribute to significant thrombotic events and pose a risk for diabetic microvascular complications. Albuminuria, one of the hallmarks of diabetes, is thought to be a risk factor for endothelial dysfunction. In this study, we investigated the association between relative thrombocytosis and an increased urine albumin-to-creatinine ratio in healthy adult participants. Using multivariate analyses on data from the Korea National Health and Nutrition Examination Survey V-VI, 12,525 eligible native Koreans aged ≥ 20 were categorized into platelet count quintiles by sex. The highest platelet count quintile included younger, more obese participants with elevated white blood cell counts, poor lipid profiles, and a better estimated glomerular filtration rate. Restricted cubic spline regression analysis revealed significant associations between platelet count and fasting blood glucose, glycated hemoglobin, and urine albumin-to-creatinine ratio. Adjusted logistic regression models indicated that heightened fasting blood glucose and platelet count were linked to risk of microalbuminuria (fasting blood glucose, odds ratio = 1.026, 95%CI = 1.011-1.042; platelet count, odds ratio = 1.004, 95%CI = 1.002-1.006). Particularly, an increased platelet count was notably associated with microalbuminuria progression in subjects with impaired fasting glucose. These findings suggest that an elevated platelet count, even below diagnostic thrombocytosis levels, independently correlates with an increased risk of vascular endothelial dysfunction in patients with impaired fasting glucose.

Nicotine Potentially Alters Endothelial Inflammation and Cell Adhesion via LGALS9.

The endothelial cell layer is essential for the maintenance of various blood vessel functions. Major risk factors for endothelial dysfunction that contribute to aortic pathologies such as abdominal aortic aneurysm (AAA) and aortic dissection (AD) include smoking tobacco cigarettes and hypertension. This study explores the effects of nicotine (Nic) and angiotensin II (Ang II) on human aortic endothelial cells (HAoECs) at a transcriptional level. HAoECs were exposed to 100 nM Nic and/or 100 nM Ang II. RNA sequencing (RNA-Seq) was performed to identify regulated genes following exposure. Results were validated applying RT-qPCR. GeneMANIA was used to perform in silico analysis aiming to identify potential downstream interacting genes in inflammatory, cell-adhesion, endothelial cell proliferation, and coagulation pathways. RNA-Seq identified LGALS9 (Galectin-9) as being potentially regulated following Nic exposure, while subsequent RT-qPCR experiments confirmed the transcriptional regulation (p < 0.05). Subsequent in silico analysis identified potential candidate genes for interacting with LGALS9 in different gene sets. Of the top 100 genes potentially interacting with LGALS9, 18 were inflammatory response genes, 28 were involved in cell adhesion, 2 in cell proliferation, and 6 in coagulation. Nic exposure of HAoECs causes a significant increase in LGALS9 at a transcriptional level. LGALS9 itself may serve as key regulator for essential endothelial cell processes via interfering with various signaling pathways and may thus represent a potentially novel target in the pathogenesis of aortic pathologies.

The Anxiety as a risk factor of endothelial dysfunction in young females during Russian-Ukrainian War

This text is the abstract of the VI Scientific and practical conference with international participation "Psychosomatic Medicine: science and practice" which took place on November 2-3, 2023 in Kyiv on the Mediamed portal.

Abstract P236: Association Of Vitamin B Deficiency-induced Hyperhomocysteinemia With Subclinical Atherosclerosis In Adolescents: Implications For Early Cardiovascular Disease Detection

In recent decades, the increased incidence of cardiovascular disease (CVD) mortality among young adults has raised concerns. Although clinical manifestations of CVD typically occur later in life, the underlying pathological processes emerge early on. Numerous studies have demonstrated that elevated homocysteine levels serve as an independent risk factor for endothelial dysfunction and arterial stiffness, which are key contributors to CVD. Notably, vitamin B deficiency, particularly deficiencies in Vitamins B9 and B12, emerges as a significant factor in childhood hyperhomocysteinemia, initiating the development of subclinical atherosclerosis in early life. In this narrative review, we summarize the association between vitamin B deficiency-induced hyperhomocysteinemia and subclinical atherosclerosis in adolescents. We conducted a comprehensive review of relevant literature from prominent bibliographic databases, including PubMed/MEDLINE, PMC Central, Google Scholar, and Cochrane database. Four cross-sectional studies were included and reviewed as part of our analysis. The reviewed studies, focusing on homocysteine levels as an exposure variable and markers of atherosclerosis as outcome measures, demonstrate a strong correlation between homocysteine levels and markers of atherosclerosis, including increased carotid intima-media thickness (CIMT) and endothelial dysfunction. Particularly, adolescents with vitamin B12 deficiency exhibit a significant positive correlation between homocysteine levels and CIMT. These findings underscore the potential of hyperhomocysteinemia as an early marker for detecting subclinical atherosclerosis in adolescents with vitamin B deficiency. Despite limited research in this area, recognizing the importance of early detection and management of subclinical atherosclerosis in adolescents can help mitigate the risk of severe cardiovascular and cerebrovascular events in young adulthood.

Cadmium exposure promotes ferroptosis by upregulating Heat Shock Protein 70 in vascular endothelial damage of zebrafish

Cadmium (Cd) exposure is a risk factor for endothelial dysfunction and cardiovascular disease. Ferroptosis is a type of cell death that relies on lipid peroxidation. Whether ferroptosis acts in Cd-induced vascular endothelial damage and the underlying mechanisms remain unclear. Herein, we found that Cd resulted in ferroptosis of vascular endothelial cells (ECs) in vivo and in vitro. In the visualized zebrafish embryos, Cd accumulated in vascular ECs, ROS and lipid peroxidation levels were increased, and the oxidoreductase system was disturbed after exposure. Moreover, Cd decreased Gpx4 in ECs and caused smaller mitochondria with increased membrane density. Accompanied by ferroptosis, the number of ECs and the area of the caudal venous plexus in zebrafish embryos were reduced, and the survival rate of HUVECs decreased. These effects were partially reversed by ferrostatin-1 and aggravated by erastin. Mechanistically, an excessive increase in Heat Shock Protein 70 (Hsp70) was identified by transcriptomics after Cd exposure. Inhibition of Hsp70 by VER-155008 or siRNA ameliorated Cd-induced ferroptosis, thereby alleviating endothelial injury. Furthermore, Hsp70 regulated Cd-induced ferroptosis by targeting multiple targets, including Gpx4, Fth1, Nrf2 and Acsl4. Our findings provide a new approach to investigating the endothelial damage of Cd and indicate that regulation of Hsp70 is an important target for alleviating this process.

Early Detection of Subclinical Atherosclerosis: Hyperhomocysteinemia as a Promising Marker in Adolescents With Vitamin B Deficiency.

In recent decades, the increased incidence of cardiovascular disease (CVD) mortality among young adults has raised concerns. Although clinical manifestations of CVD typically occur later in life, the underlying pathological processes emerge early on. Thisreview article summarizesthe association between vitamin B deficiency-induced hyperhomocysteinemia and subclinical atherosclerosis in adolescents. Numerous studies have demonstrated that elevated homocysteine levels are an independent risk factor for endothelial dysfunction (ED) and arterial stiffness, which are key contributors to CVD. Notably, vitamin B deficiency, particularly in vitaminB9 and vitamin B12, emerges as a significant factor in childhood hyperhomocysteinemia, initiating the development of subclinical atherosclerosis in early life. A comprehensivereview of relevant literature from prominent bibliographic databases, including PubMed/MEDLINE, PubMed Central, Google Scholar, and Cochrane, was performed. Four cross-sectional studiesfocusing on homocysteine levels as an exposure variable and markers of atherosclerosis as outcome measureswere included and reviewed as part of our analysis. The reviewed studies demonstrate apositive correlation between homocysteine levels and markers of atherosclerosis, including increased carotid intima-media thickness (CIMT) and ED.Mainly, adolescents with vitamin B12 deficiency exhibit a significant positive correlation between homocysteine levels and CIMT. These findings underscore the potential of hyperhomocysteinemia as an early marker for detecting subclinical atherosclerosis in adolescents with vitamin B deficiency.Despite limited research in this area, recognizing the importance of early detection and management of subclinical atherosclerosis in adolescents can help mitigate the risk of severe cardiovascular events such as myocardial infarction and stroke in young adulthood.

The effect of exenatide (a GLP-1 analogue) and sitagliptin (a DPP-4 inhibitor) on asymmetric dimethylarginine (ADMA) metabolism and selected biomarkers of cardiac fibrosis in rats with fructose-induced metabolic syndrome

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, is a risk factor for endothelial dysfunction, a common pathophysiological denominator for both atherogenesis and cardiac fibrosis.We aimed to investigate whether the cardioprotective and antifibrotic effects of incretin drugs, exenatide and sitagliptin, may be associated with their ability to affect circulating and cardiac ADMA metabolism.Normal and fructose-fed rats were treated with sitagliptin (5.0/10 mg/kg) or exenatide (5/10 µg/kg) for 4 weeks. The following methods were used: LC-MS/MS, ELISA, Real-Time-PCR, colorimetry, IHC and H&E staining, PCA and OPLS-DA projections.Eight-week fructose feeding resulted in an increase in plasma ADMA and a decrease in NO concentration. Exenatide administration into fructose-fed rats reduced the plasma ADMA level and increased NO level. In the heart of these animals exenatide administration increased NO and PRMT1 level, reduced TGF-ß1, α-SMA levels and COL1A1 expression. In the exenatide treated rats renal DDAH activity positively correlated with plasma NO level and negatively with plasma ADMA level and cardiac α-SMA concentration. Sitagliptin treatment of fructose-fed rats increased plasma NO concentration, reduced circulating SDMA level, increased renal DDAH activity and reduced myocardial DDAH activity. Both drugs attenuated the myocardial immunoexpression of Smad2/3/P and perivascular fibrosis.In the metabolic syndrome condition both sitagliptin and exenatide positively modulated cardiac fibrotic remodeling and circulating level of endogenous NOS inhibitors but had no effects on ADMA levels in the myocardium.

Noise, Air, and Heavy Metal Pollution as Risk Factors for Endothelial Dysfunction.

During the last two decades, large epidemiological studies have shown that the physical environment, including noise, air pollution or heavy metals, have a considerable impact on human health. It is known that the most common cardiovascular risk factors are all associated with endothelial dysfunction. Vascular tone, circulation of blood cells, inflammation, and platelet activity are some of the most essential functions regulated by the endothelium that suffer negative effects as a consequence of environmental pollution, causing endothelial dysfunction. In this review, we delineate the impact of environmental risk factors in connection to endothelial function. On a mechanistic level, a significant number of studies suggest the involvement of endothelial dysfunction to fundamentally drive the adverse endothelium health effects of the different pollutants. We focus on well-established studies that demonstrate the negative effects on the endothelium, with a focus on air, noise, and heavy metal pollution. This in-depth review on endothelial dysfunction as a consequence of the physical environment aims to contribute to the associated research needs by evaluating current findings from human and animal studies. From a public health perspective, these findings may also help to reinforce efforts promoting the research for adequate promising biomarkers for cardiovascular diseases since endothelial function is considered a hallmark of environmental stressor health effects.

Evaluation of Maternal Serum Homocysteine in Pre eclampsia

Background: Pre-eclampsia affects about 2–8% of all pregnancies. It is one of the leading causes of maternal and perinatal morbidity and mortality hyperhomocysteinemia is considered as a risk factor for endothelial dysfunction and vascular disease. The vascular changes induced by homocysteine are similar to those with pre-eclampsia. The aim of the study is to identify the relationship between maternal serum homocysteine level and the development of pre-eclampsia.Method and patient: A case control study that was carried out in the Department of Obstetrics and Gynecology at Azadi Teaching Hospital in Kirkuk-Iraq, during the period of eight months from 1st of Feb. till 1st of October 2021. It included 80 pregnant women with singleton viable pregnancy, gestational age of > 20 weeks. They were divided into two groups: Case group included 40 pregnant women who had diagnosed as pre eclampsia (mild and severe) and control group included 40 healthy normotensive pregnant women. Patients with multiple pregnancy, history of medical disease or tacking treatment for hypertension were excluded from the study. Blood sample was taken from each woman for biochemical study, serum homocysteine level was measured using ELISA technique.Result: In this study, pregnant women with pre-eclampsia had significantly higher mean of serum homocysteine compared with controls. Homocysteine level > 8.95 μmol/l is a predictor for pre-eclampsia. Out of 40 women with pre-eclampsia, 42.5% were mild, while the remaining 57.5% were severe. Pregnant women with severe pre eclampsia had significantly higher mean of serum homocysteine compared to those with mild pre-eclampsia. The level of tested biomarkers and homocysteine was tested between the two study groups to assess their rule in pre eclampsia.Conclusions: Maternal serum homocysteine biomarker represents an early non-invasive marker for diagnosis of pre eclampsia and to name the disease according to the severity.

Impaired β 2 -adrenergic endothelium-dependent vasodilation in patients previously hospitalized with coronavirus disease 2019.

The pulse wave response to salbutamol (PWRS) - change in augmentation index (AIx) - provides a means to assess endothelial vasodilator function in vivo . Endothelial dysfunction plays a relevant role in the pathogenesis of hypertension and cardiovascular disease and appears to underlie many of the complications of coronavirus disease 2019 (COVID-19). However, to what degree this persists after recovery is unknown. Individuals previously hospitalized with COVID-19, those recovered from mild symptoms and seronegative controls with well known risk factors for endothelial dysfunction were studied. To assess the involvement of nitric oxide-cyclic guanosine monophosphate pathway (NO-cGMP) on PWRS, sildenafil was also administrated in a subsample. One hundred and one participants (60 men) aged 47.8 ± 14.1 (mean ± SD) years of whom 33 were previously hospitalized with COVID-19 were recruited. Salbutamol had minimal effect on haemodynamics including blood pressure and heart rate. It reduced AIx in controls ( n = 34) and those recovered from mild symptoms of COVID-19 ( n = 34) but produced an increase in AIx in those previously hospitalized: mean change [95% confidence interval] -2.85 [-5.52, -0.188] %, -2.32 [-5.17,0.54] %, and 3.03 [0.06, 6.00] % for controls, those recovered from mild symptoms and those previously hospitalized, respectively ( P = 0.001). In a sub-sample ( n = 22), sildenafil enhanced PWRS (change in AIx 0.05 [-2.15,2.24] vs. -3.96 [-7.01. -2.18], P = 0.006) with no significant difference between hospitalized ( n = 12) and nonhospitalized participants ( n = 10). In patients previously hospitalized with COVID-19, there is long-lasting impairment of endothelial function as measured by the salbutamol-induced stimulation of the NO-cGMP pathway that may contribute to cardiovascular complications.

Acute effects of online hemodiafiltration versus high-flux hemodialysis on serum levels of asymmetric dimethylarginine and tumor necrosis factor-alpha

Background Chronic inflammation as a major determinant of ‘dialysis syndrome’ is considered as the main factor of morbidity and mortality in dialysis patients. Tumor necrosis factor-alpha (TNF-α) may play important roles in the development of T helper (Th) imbalance, cardiovascular disease, and wasting in the uremic milieu. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide that may be an independent risk factor for endothelial dysfunction and cardiovascular disease. In hemodialysis (HD) patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. The aim of this study to evaluate the acute effects of hemodiafiltration (HDF) compared with conventional HD on blood levels of ADMA and TNF-α. Patients and methods A cross-sectional study was conducted on 20 patients with end-stage renal disease receiving dialysis in the dialysis unit of Ain Shams Specialized Hospital receiving twice weekly HD session with high-flux (HF) dialyzer and once weekly HDF session. Blood samples were collected from all participants before and after HD session and from the same participants before and after HDF session. ADMA and TNF-α levels were assessed by enzyme-linked immunosorbent assay techniques. Results The decrease in TNF-α was higher after HDF session versus HF HD session (79.47 ± 14.16 vs. 50.43 ± 31.05), with P value of 0.001. Moreover, the decrease in ADMA was higher after HDF session versus HF HD session (75.01 ± 12.55 vs. 41.79 ± 24.73), with P value of 0.001. Conclusion The use of online HDF technique showed a significant reduction of ADMA and TNF-α in adults with end-stage renal disease.

Endothelial dysfunction: developmental mechanisms and therapeutic strategies

Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious.&#x0D; The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angio­genesis, vascular tone, and permeability.&#x0D; Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction.&#x0D; Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endo­thelial dysfunction.&#x0D; Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology.&#x0D; Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described.&#x0D; Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.

Uric Acid Induces a Proatherothrombotic Phenotype in Human Endothelial Cells by Imbalancing the Tissue Factor/Tissue Factor Pathway Inhibitor Pathway.

Several evidence show that elevated plasma levels of uric acid (UA) are associated with the increased risk of developing atherothrombotic cardiovascular events. Hyperuricemia is a risk factor for endothelial dysfunction (ED). ED is involved in the pathophysiology of atherothrombosis since dysfunctional cells lose their physiological, antithrombotic properties. We have investigated whether UA might promote ED by modulating the tissue factor (TF)/TF pathway inhibitor (TFPI) balance by finally changing the antithrombotic characteristics of endothelial cells. Human umbilical vein endothelial cells were incubated with increasing doses of UA (up to 9 mg/dL). TF gene and protein expressions were evaluated by real-time polymerase chain reaction (PCR) and Western blot. Surface expression and procoagulant activity were assessed by FACS (fluorescence activated cell sorting) analysis and coagulation assay. The mRNA and protein levels of TFPI were measured by real-time PCR and Western blot. The roles of inflammasome and nuclear factor-κB (NF-κB) as possible mechanism(s) of action of the UA on TF/TFPI balance were also investigated. UA significantly increased TF gene and protein levels, surface expression, and procoagulant activity. In parallel, TFPI levels were significantly reduced. The NF-κB pathways appeared to be involved in modulating these phenomena. Additionally, inflammasome might also play a role. The present in vitro study shows that one of the mechanisms by which high levels of UA contribute to ED might be the imbalance between TF/TFPI levels in endothelial cells, shifting them to a nonphysiological, prothrombotic phenotype. These UA effects might hypothetically explain, at least in part, the relationship observed between elevated plasma levels of UA and cardiovascular events.

Protective Effect of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) against Vascular Dysfunction in Hyperglycemic Rats.

Hyperglycemia is a major risk factor for endothelial dysfunction. Endothelial dysfunction is associated with the inability of endothelial cells to maintain homeostasis of the cardiovascular system. Regular exercise may be considered as an effective and low-cost nonpharmacological tool for improving vascular function, though there is no agreement on the best type of exercise. To determine how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) may prevent endothelial dysfunction under hyperglycemic conditions, and to compare these two interventions. Twenty-four eight-week-old male Wistar rats were randomly assigned into four groups: healthy nonexercising control (C), hyperglycemic control (HG-C), hyperglycemic + HIIT (HG-IT), and hyperglycemic + MICT (HG-CT). Hyperglycemia was induced by a single injection of streptozotocin. Hyperglycemic animals were subjected to HIIT or MICT protocols six days a week for six weeks. Decapitation was performed the day after the exercise protocols were completed. The ascending aorta (until the abdominal artery) was examined. An enzyme-linked immunosorbent assay (ELISA) was used to measure the glucagon-likepeptide-1 (GLP-1), endothelial nitric oxide synthase (eNOS), and tumor necrosis factor-alpha (TNFα) levels. A colorimetric assay was used to measure superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels. Quantitative real-time polymerase chain reaction (PCR) was used to measure the expression of the receptor for advanced glycation end-products (RAGE) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Hematoxylin and eosin (H&E) staining was used to histologically analyze the aortas. There was a significantly higher level of GLP-1 and lower expression of RAGE, NF-κB, and TNFα in the HG-IT and HG-CT group compared to the HG-C group. Microscopic examination of aortic tissue showed a better tissue arrangement in both treatment groups than in the HG-C group. Except for the MDA level, there were no significant differences in any of the measured parameters between the HG-IT and HG-CT groups. Under hyperglycemic conditions, both HIIT and MICT have a protective role against endothelial dysfunction.

Bronchial Asthma as a Cardiovascular Risk Factor: A Prospective Observational Study.

Introduction: Asthma as a chronic inflammatory disorder has been suggested as a risk factor for endothelial dysfunction (ED), but studies on the association between asthma and cardiovascular disease (CVD) risk are limited. Background: We assessed associations of ED with the severity of asthma, eosinophilic inflammation, lung function, and asthma control. Methods: 52 young asthmatics (median age of 25.22 years) and 45 healthy individuals were included. Demographic, clinical, and laboratory findings were recorded. We evaluated microvascular responsiveness by recording the reactive hyperemia index (RHI) indicating post-occlusive peripheral endothelium-dependent changes in vascular tone using the Itamar Medical EndoPAT2000. VCAM-1, ADMA, high-sensitive CRP (hsCRP), and E-selectin were measured. Results: Asthmatics had considerably lower RHI values (p < 0.001) with a dynamic decreasing trend by asthma severity and higher hsCRP levels (p < 0.001). A substantial increase in hsCRP and E-selectin with asthma severity (p < 0.05) was also observed. We confirmed a higher body mass index (BMI) in asthmatics (p < 0.001), especially in women and in severe asthma. Conclusions: We demonstrated the progression of CVD in asthmatics and the association of the ongoing deterioration of ED with the inflammatory severity, suggesting that the increased risk of CVD in young asthmatics is dependent on disease severity. The underlying mechanisms of risk factors for CVD and disease control require further study.

Effect of troxerutin in counteracting hyperglycemia-induced VEGF upregulation in endothelial cells: a new option to target early stages of diabetic retinopathy?

Diabetic retinopathy (DR), one of the most common complications of diabetes mellitus, is characterized by degeneration of retinal neurons and neoangiogenesis. Until today, the pharmacological approaches for DR are limited and focused on counteracting the end-stage of this neurodegenerative disease, therefore efforts should be carried out to discover novel pharmacological targets useful to prevent DR development. Hyperglycemia is a major risk factor for endothelial dysfunction and vascular complication, which subsequently may trigger neurodegeneration. We previously demonstrated that, in the rat retina, hyperglycemia activates a new molecular cascade implicating, up-stream, protein kinase C βII (PKC βII), which in turn leads to a higher expression of vascular endothelial growth factor (VEGF), via the mRNA-binding Hu-antigen R (HuR) protein. VEGF is a pivotal mediator of neovascularization and a well-known vasopermeability factor. Blocking the increase of VEGF via modulation of this cascade can thus represent a new pharmacological option to prevent DR progression. To this aim, proper in vitro models are crucial for drug discovery, as they allow to better identify promising effective molecules. Considering that endothelial cells are key elements in DR and that hyperglycemia triggers the PKCβII/HuR/VEGF pathway, we set up two distinct in vitro models applying two different stimuli. Namely, human umbilical vein endothelial cells were exposed to phorbol 12-myristate 13-acetate, which mimics diacylglycerol whose synthesis is triggered by diabetic hyperglycemia, while human retinal endothelial cells were treated with high glucose for different times. After selecting the optimal experimental conditions able to determine an increased VEGF production, in search of molecules useful to prevent DR development, we investigated the capability of troxerutin, an antioxidant flavonoid, to counteract not only the rise of VEGF but also the activation of the PKCβII/HuR cascade in both in vitro models. The results show the capability of troxerutin to hinder the hyperglycemia-induced increase in VEGF in both models through PKCβII/HuR pathway modulation. Further, these data confirm the key engagement of this cascade as an early event triggered by hyperglycemia to promote VEGF expression. Finally, the present findings also suggest the potential use of troxerutin as a preventive treatment during the early phases of DR.

Preoperative Vascular Function Assessment and Perioperative Vascular Events in Patients Posted for Elective Non-cardiac Surgeries.

BackgroundCoronary atherosclerosis is usually asymptomatic until a major cardiac event occurs. Surgery is one of the major stress factors that play a role in hastening vascular deterioration in susceptible patients. Non-invasive tests to detect atherosclerosis and endothelial dysfunction have started gaining popularity nowadays, and of the several options, carotid artery intima-media thickness (IMT) and radial artery flow-mediated dilation (FMD) are two promising tests for detecting cardiovascular impairment.MethodsThis was a pilot study that was undertaken on 100 patients in a tertiary care medical center (Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry) between June 2015 and August 2016 with the aim of studying the prevalence of endothelial dysfunction and early atherosclerosis in the given population, and to find out the predictive power of preoperative vascular functional assessment in the prediction of perioperative cardiovascular events in the same population. We had selected patients who had at least two risk factors for endothelial dysfunction and were posted for elective non-cardiac surgical procedures via convenience sampling. Flow-mediated vasodilatation of the radial artery (FMD) and carotid intima-media thickness (CIMT) were measured on the previous day of surgery, while a fasting lipid profile was collected from the patients on the morning of the surgery. Endothelial dysfunction was defined as FMD<4.5%, while atherosclerosis was defined as CIMT>0.07 cm. Demographic details and baseline hemodynamic parameters of the patients were also noted preoperatively as well as intra-operatively, and patients were followed up for any major clinical adverse cardiovascular event post-operatively till they were discharged from the hospital.ResultsIt was found that the prevalence of endothelial dysfunction was 23%, while the prevalence of early atherosclerosis was 33% in our study population. However, it was found that FMD and CIMT did not correlate with each other significantly, nor did they correlate significantly with perioperative cardiovascular events. The risk factors of the patients also did not correlate with the FMD and CIMT values of the patients in which they were impaired. Moreover, they did not have any significant correlation with the perioperative events that occurred.ConclusionThe prevalence of endothelial dysfunction in our tertiary center was found to be 23%, and the prevalence of atherosclerosis was 33% in patients posted for elective non-cardiac surgery who had multiple risk factors. It was also found that non-invasive preoperative vascular assessment was not quite effective as hypothesized in predicting perioperative cardiovascular events.

Effects of Blueberry Consumption on Cardiovascular Health in Healthy Adults: A Cross-Over Randomised Controlled Trial.

Blueberries are rich in polyphenols, and their effect on cardiovascular health, including risk factors for endothelial dysfunction and hypertension, has been investigated in interventional studies. However, the difference between blueberry treatments in varied forms for their cardiovascular-protective effect remains poorly understood. The current study assessed the effects of whole blueberry and freeze-dried blueberry powder compared to a control on cardiovascular health in young adults. A cross-over randomised controlled trial (RCT) was implemented with 1 week of treatment for three treatment groups, each followed by 1 week of wash out period. Systolic (SBP) and diastolic blood pressure (DBP), pulse wave velocity (PWV), plasma cholesterol (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol) and triglyceride levels (TAG), and glucose and nitrite (NO2-) concentrations were compared following fresh blueberry, freeze-dried blueberry powder, and control treatments. Thirty-seven participants with a mean age of 25.86 ± 6.81 completed the study. No significant difference was observed among fresh blueberry, blueberry powder, and the control arm. Plasma NO2- levels were improved by 68.66% and 4.34% separately following whole blueberry and blueberry powder supplementations compared to the baseline, whereas the control supplementation reported a decrease (−9.10%), although it was not statistically significant. There were no other effects shown for SBP, DBP, total cholesterol, HDL-C, LDL-C, TAG, or glucose. No difference was shown between whole blueberry and freeze-dried blueberry powder consumption for improving cardiovascular health.

PD22-11 SUBCLINICAL INFLAMMATION AS A PREDICTOR FOR ERECTILE DYSFUNCTION AFTER BRACHYTHERAPY FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD22-11 SUBCLINICAL INFLAMMATION AS A PREDICTOR FOR ERECTILE DYSFUNCTION AFTER BRACHYTHERAPY FOR LOCALIZED PROSTATE CANCER Laurianne Rita Garabed, Daniel Taussky, Guila Delouya, and Daniel Liberman Laurianne Rita GarabedLaurianne Rita Garabed More articles by this author , Daniel TausskyDaniel Taussky More articles by this author , Guila DelouyaGuila Delouya More articles by this author , and Daniel LibermanDaniel Liberman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). Treatment of localized prostate cancer (PCa) is also associated with a greater risk of ED. In this study, we aimed to determine the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa. METHODS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. Patient characteristics and erectile function at last follow-up were compared for patients with a baseline NLR<2 and ≥2. Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED. RESULTS: Baseline NLR≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p=0.002) and multivariate analyses (p=0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 group, compared to 29% for the NLR <2 group. CONCLUSIONS: In a large cohort of patients with PCa who underwent PB, it was found that NLR was a predictor of post-treatment ED, even after adjusting for available covariates, including age and known risk factors for endothelial dysfunction. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e408 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Laurianne Rita Garabed More articles by this author Daniel Taussky More articles by this author Guila Delouya More articles by this author Daniel Liberman More articles by this author Expand All Advertisement PDF DownloadLoading ...