Vascular Endothelial Dysfunction In Patients Research Articles

The role and mechanism of RIPK1 in vascular endothelial dysfunction in chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and cardiovascular events, but the mechanism is unclear. In our study, we found elevated levels of RIPK1 in patients with CKD and cardiovascular events through bioinformation analysis. Elevated RIPK1 levels were found in serum samples of CKD patients and were associated with vascular endothelial dysfunction and renal function. We constructed the five of six nephrectomy of CKD mice model, finding that RIPK1 expressions were elevated in abdominal aorta endothelial cells. After RIPK1 inhibition and overexpression, it was found that RIPK1 could regulate the expression of endothelial nitric oxide synthase (eNOS) and cell adhesion molecule 1 (ICAM-1), and activation of inflammatory responses and endoplasmic reticulum (ER) stress. In addition, uremic toxin induced abnormal expression of RIPK1 invitro. We observed RIPK1-mediating endothelial dysfunction and inflammation responses by ER stress pathways through gain and loss of function. In order to explore the specific mechanism, we conducted co-immunoprecipitation and expression regulation of RIPK1 and IKK, finding that RIPK1 formed complex with IKK and regulated IKK expression. In conclusion, we demonstrated that RIPK1 levels were closely associated with vascular endothelial dysfunction in patients with CKD. With uremic toxins, RIPK1 expression was elevated, which led to the activation of inflammation through the ER stress pathway, resulting in vascular endothelial injury. Besides, activation of RIPK1-IKK-NF-κB axis was a key driver of endothelial dysfunction in CKD. Our study provides a new perspective for the study of cardiovascular events in CKD.

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.

Serum endocan levels in patients with habitual abortion.

The aim of this study was to investigate whether there is a new factor in the etiology of recurrent loss of pregnancy. For this purpose, serum malondialdehyde (MDA) and nitric oxide (NO) levels as indicators of oxidative stress, and endocan levels, a marker of vascular dysfunction, were investigated in patients diagnosed with habitual abortion. The research was conducted as a prospective case-control study. Patients aged 18-40 years with two or more consecutive pregnancy losses revealed by ultrasonographic or histopathological examination, and with no pathology capable of causing habitual abortion were included in the study group. Patients with no history of abortion, with at least one healthy pregnancy, who were planning pregnancies, and who presented to the outpatient clinic for routine prepregnancy tests were selected as the control group. Two groups were established-habitual abortion (n = 30) and control (n = 29). At the end of the menstrual cycle, blood samples were collected and centrifuged. Serum NO, MDA, and endocan levels were studied. Serum endocan, NO, and MDA levels were higher in women with habitual abortion compared to healthy controls. Pearson's correlation analysis revealed a positive correlation between serum endocan levels and NO and MDA levels. A positive correlation was also observed between serum MDA and NO levels. Multiple regression was run to predict serum endocan levels from MDA and NO levels. These variables emerged as statistically significant predictors of endocan. These findings suggest the presence of vascular endothelial dysfunction in patients with habitual abortion.

Circulating Serum Cystatin C as an Independent Risk Biomarker for Vascular Endothelial Dysfunction in Patients with COVID-19-Associated Multisystem Inflammatory Syndrome in Children (MIS-C): A Prospective Observational Study.

Multisystem inflammatory syndrome in children (MIS-C) is a new clinical entity that has emerged in the context of the COVID-19 pandemic. Despite the less severe course of the disease, varying degrees of cardiovascular events may occur in MIS-C; however, data on vascular changes occurring in MIS-C are still lacking. Endothelial dysfunction (ED) is thought to be one of the key risk factors contributing to MIS-C. We conducted a prospective observational study. We investigated possible manifestations of cardiac and endothelial involvement in MIS-C after the treatment of the acute stage and potential predictive biomarkers in patients with MIS-C. Twenty-seven consecutive pediatric subjects (≥9 years), at least three months post-treated MIS-C of varying severity, in a stable condition, and twenty-three age- and sex-matched healthy individuals (HI), were enrolled. A combined non-invasive diagnostic approach was used to assess endothelial function as well as markers of organ damage using cardiac examination and measurement of the reactive hyperemia index (RHI), by recording the post- to pre-occlusion pulsatile volume changes and biomarkers related to ED and cardiac disease. MIS-C patients exhibited a significantly lower RHI (indicative of more severe ED) than those in HI (1.32 vs. 1.80; p = 0.001). The cutoff of RHI ≤ 1.4 was independently associated with a higher cardiovascular risk. Age and biomarkers significantly correlated with RHI, while serum cystatin C (Cys C) levels were independently associated with a diminished RHI, suggesting Cys C as a surrogate marker of ED in MIS-C. Patients after MIS-C display evidence of ED, as shown by a diminished RHI and altered endothelial biomarkers. Cys C was identified as an independent indicator for the development of cardiovascular disease. The combination of these factors has the potential to better predict the cardiovascular consequences of MIS-C. Our study suggests that ED may be implicated in the pathophysiology of this disease.

LncRNA ANRIL mediates endothelial dysfunction through BDNF downregulation in chronic kidney disease

Endothelial dysfunction is common in patients with chronic kidney disease (CKD), but the mechanism is unknown. In this study, we found that the circulating ANRIL level was increased and correlated with vascular endothelial dysfunction in patients with CKD, also negatively correlated with plasma brain-derived neurotrophic factor (BDNF) concentration. We constructed the ANRIL knockout mice model, and found that ANRIL deficiency reversed the abnormal expression of BDNF, along with endothelial nitric oxide synthase (eNOS), vascular adhesion molecule 1 (VCAM-1) and Von Willebrand factor (vWF). Meanwhile, mitochondrial dynamics-related proteins, Dynamin-related protein 1 (Drp1) and mitofusins (Mfn2) level were also recovered. In addition, in vitro, serum derived from CKD patients and uremia toxins induced abnormal expression of ANRIL. By making use of the gain- and loss-of-function approaches, we observed that ANRIL mediated endothelial dysfunction through BDNF downregulation. To explore the specific mechanism, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) were used to explore the binding of ANRIL to histone methyltransferase Enhancer of zeste homolog 2 (EZH2). Further experiments found increased EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) levels at the BDNF promoter region. Collectively, we demonstrated that ANRIL mediate BDNF transcriptional suppression through recruitment of EZH2 to the BDNF promoter region, then regulated the proteins expression related to endothelial function and mitochondrial dynamics. This study provides new insights for the study of endothelial dysfunction in CKD.

Efficacy of Shexiang Tongxin Dropping Pills in a Swine Model of Coronary Slow Flow.

Objective: Preliminary clinical studies have confirmed that Shexiang Tongxin dropping pills (STDPs) could improve angina pectoris and attenuate vascular endothelial dysfunction in patients with slow coronary flow, but the underlying mechanism is not fully unclear. We aimed to investigate the impact of STDP in a swine model of coronary slow flow (SF) and related mechanisms. Methods: SF was induced by coronary injection of microspheres, and pigs were randomly divided into the SF group and SF plus STDP group. Pigs in the STDP group received sublingual STDP for 10 min, followed by 1 g STDP oral administration daily for 6 days. Coronary angiography was performed, the TIMI frame count (TFC) was determined, and hemodynamic measurements were performed before, at 30 min, and 7 days post-SF. Serum levels of total NO, NOS, ET-1, C-TNI, and BNP were measured. Myocardial expressions of TNF and IL-6, eNOS, VEGF, CD31, and α-SMA were analyzed by immunohistochemistry and Western blotting. Results: Compared to the SF group, LVEF and TFC were significantly improved at 7 days post-SF in the STDP group. The serum ET-1 level was significantly reduced at 7 days, and NO and NOS levels were significantly higher in the STDP group. Seven days post-SF, myocardial TNF and IL-6 expressions were significantly downregulated, while the expressions of eNOS and VEGF, CD31, and ɑ-SMA were significantly upregulated in the STDP group. Conclusion: Our results showed that STDP improved cardiac function and coronary flow, possibly through reducing inflammatory responses and upregulating myocardial eNOS and VEGF, CD31, and the ɑ-SMA expression.

Vitamin E reduces inflammation and improves cognitive disorder and vascular endothelial functions in patients with leukoaraiosis

Background Leukoaraiosis (LA) is a disease manifested by demyelination and gliosis in white matter, mainly caused by cerebrovascular diseases. LA is closely related to the expression level of inflammatory factors, oxidative stress, and vascular endothelial dysfunction in patients. Vitamin E may play antioxidant and anti-inflammatory roles in various diseases. We aimed to explore the effects of vitamin E on the patients with LA. Methods A total of 160 patients with LA were recruited in this research. Matrix metalloproteinase-9 (MMP-9), MMP-2, C-reactive protein (CRP), complement 3 (C3), C4, nitric oxide (NO), and endothelin (ET) levels were evaluated by ELISA. The Mini-Mental State Examination (MMSE) was used for cognitive impairment assessment. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were analyzed by commercial kits. Results The levels of CRP, C3, and C4 significantly decreased in the serum of LA patients after the administration of vitamin E. The levels of MMP-2 and MPP-9 showed a significant decrease in the administered group. Vitamin E significantly inhibited the expression of MDA, while significantly upregulated the expression of SOD. Significant increase in NO production and significant downregulation of ET expression occurred in vitamin E groups. MMSE score was significantly increased by vitamin E. Conclusion In conclusion, vitamin E showed effects on the alleviation of inflammatory response, oxidative stress, endothelial damage, and cognitive dysfunction. Thus, vitamin E could be a potential drug for the clinical treatment of LA patients.

Association of enhanced circulating trimethylamine N-oxide with vascular endothelial dysfunction in periodontitis patients.

Accumulating evidences indicate that periodontitis is closely associated with endothelial dysfunction. Trimethylamine-N-oxide (TMAO), a harmful microbiota generated metabolite, has been implicated as a nontraditional risk factor for impaired endothelial function. However, whether increased circulating levels of TMAO in periodontitis patients induces endothelial dysfunction remains unknown. Patients with periodontitis and periodontally healthy controls were enrolled. Periodontal inflamed surface area (PISA) was calculated to assess the inflammatory burden posed by periodontitis. The circulating TMAO was measured by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Vascular endothelial function including peripheral endothelial progenitor cells (EPCs), brachial arterial flow-mediated vasodilation (FMD), and brachial-ankle pulse wave velocity (baPWV) were assessed. We also isolated and cultured EPCs from participants' peripheral blood to investigate the effect of TMAO on EPC functions in vitro. One hundred and twenty two patients with Stage III-IV periodontitis and 81 healthy controls were included. Patients with periodontitis presented elevated TMAO (P=0.002), lower EPCs (P=0.025), and declined FMD levels (P=0.005). The TMAO concentrations were correlated with reduced circulating EPCs and FMD levels. Moreover, TMAO can injury EPCs function in vitro, and may induce cell pyroptosis via Bax/caspase-3/GSDME pathway. The present study demonstrates for the first time that circulating TMAO levels are increased in patients with Stage III-IV periodontitis, and correlated with vascular endothelial dysfunction. These findings may provide a novel insight into the mechanism of vascular endothelial dysfunction in patient with periodontitis via TMAO-downregulated EPC functions.

Improvement of Vascular Endothelial Function Reflects Nonrecurrence After Catheter Ablation for Atrial Fibrillation.

BackgroundThe clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia‐peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF.Methods and ResultsConsecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia‐peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P=0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P=0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log‐rank test, P<0.001).ConclusionsThe presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia‐peripheral arterial tonometry. Long‐term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.

THE PROBLEM OF POSTOPERATIVE COGNITIVE DYSFUNCTION IN PATIENTS WITH OBESITY IN EMERGENCY SURGERY

The occurrence of postoperative cognitive dysfunction is a negative consequence of vascular endothelial dysfunction in patients with grade I-II obesity with appropriate metabolic shifts and comorbid background, which increases the duration of treatment and worsens the prognosis in patients with acute surgical pathology. It is important to add endothelioprotectors to the intensive care unit. L-arginine hydrochloride has been shown to be pathogenetically justified as a prophylaxis for an increase in the level of antigens to von Willebrand factor in the blood of obese patients with acute surgical pathology. Administration of this substance before and during surgery is likely to improve mental performance in the postoperative period in patients with elevated body mass index, who underwent emergency cholecystectomy.

Low Vitamin D Levels are Associated with Vascular Endothelial Dysfunction in Patients with Poorly Controlled Type 2 Diabetes: A Retrospective Study.

Aim: This study aimed to determine the association between serum 25-hydroxyvitamin D (25(OH)D) levels and vascular endothelial function in patients with type 2 diabetes (T2D). Methods: This retrospective study included 113 patients with poorly controlled T2D who were admitted for in-hospital diabetes educational program and underwent measurements of serum 25(OH)D levels and reactive hyperemia index (RHI). Results: Serum 25(OH)D levels significantly correlated with RHI in T2D patients. Receiver operating characteristic (ROC) curve analysis showed that serum 25(OH)D level of 16.5 ng/mL is the optimal cutoff level for predicting vascular endothelial dysfunction (RHI＜1.67), with a sensitivity of 68.5%, specificity of 67.9%, and area under the ROC curve of 0.668 (95% confidence interval [CI]: 0.566–0.770, p =0.002). The mean RHI was significantly lower (1.70±0.54) in patients with low 25(OH)D levels ( n =56, 25(OH)D levels ＜16.5 ng/mL) than that (1.99±0.58; p ＜0.001) in patients with high 25(OH)D levels ( n =57, 25(OH)D level ≥ 16.5 ng/mL). The proportion of patients with RHI＜1.67 was higher in the low 25(OH)D group than in the high 25(OH)D group (38% vs. 18%; p ＜0.001). Multivariate logistic regression analysis identified that serum 25(OH)D level ＜16.5 ng/mL was associated with increased odds of RHI ＜1.67 (odds ratio 4.598, 95% CI 1.961–10.783, p ＜0.001). Conclusion: The results demonstrated the association of serum 25(OH)D levels with endothelial function in poorly controlled T2D patients and identified serum 25(OH)D level of ＜16.5 ng/mL as a predictor of RHI ＜1.67. Serum 25(OH)D level is a potentially useful marker of vascular endothelial dysfunction in poorly controlled T2D patients.

CONDITION OF ENDOTHELIAL FUNCTIONS OF VASCULAR WALL IN HYPERTENSIVE PATIENTS DURING DENTAL IMPLANTATION

Preoperative correction of periodontal vascular endothelial dysfunction in patients with essential hypertension (HD) can improve the efficiency of dental interventions and reduce the incidence of complications during the implantation process. The periodontal status and functional state of the vascular endothelium were examined in 60 patients with essential hypertension, aged 35 to 45, before and after implantation. The first, main group included 40 people with hypertension, who, in preparation for implantation, along with traditional dental treatment, were prescribed an antioxidant drug Mexidol. Patients of the main group were divided into two subgroups: in subgroup A, a solution of Mexidol was used in the form of applications on the mucous membrane of the gums; in subgroup B, the drug was administered both locally and per os. In the second group, in 20 patients with hypertension, surgical intervention was performed after the traditional complex of therapy. The control group consisted of 10 apparently healthy patients of the same age, with normal blood pressure. Endothelial dysfunction was diagnosed by the level of stable end metabolites of nitric oxide. During the initial examination of patients with hypertension, a significant decrease in the content of nitric oxide metabolites in the blood serum was revealed in comparison with the indicators of patients in the control group. After the course of the therapy, the indicators of nitric oxide in the serum of patients with hypertension increased, more significantly in those who received Mexidol, both locally and orally, which was accompanied by a clear improvement in periodontal status and the absence of complications in the postoperative period.

The role of nitric oxide (NO) levels in patients with obstructive sleep apnea-hypopnea syndrome: a meta-analysis.

The pathogenesis of cardiovascular disease (CVD) in patients with obstructive sleep apnea (OSA) is unclear. Several studies have suggested that CVD may be caused by oxidative stress from chronic intermittent hypoxia and associated vascular endothelial dysfunction. Oxidative stress in patients with OSA can induce endothelial cell apoptosis, aggravate vascular endothelial damage, and promote the expression of redox-sensitive genes and adhesion molecules. No meta-analysis has explored whether or not OSA is related to nitric oxide (NO). To assess the association between serum/plasma NO levels and OSA, we performed a meta-analysis of the literature on the subject to grade the strength of evidence. OSA was significantly related to decreased serum or plasma NO levels (WMD = - 11.66, 95% CI - 17.21 to - 6.11; P< 0.01). Among the studies analyzed, there was high degree of heterogeneity (I2 = 79%, P< 0.01). Sensitivity analysis showed that after omitting any single study or converting a random effects model (REM) to a fixed effects model (FEM), the main results still held. This meta-analysis suggests a strong correlation between OSA and serum or plasma NO levels which may explain the link between intermittent hypoxia of OSA and risk of CVD. The strength of this finding may spur further basic and clinical research into vascular endothelial dysfunction in patients with OSA.

Plant-Based Diet Reverses Vascular Endothelial Dysfunction in Patients with Peripheral Arterial Disease

OBJECtIVE: Peripheral arterial disease (PAD) is characterized by impaired arterial circulation to the extremities caused in part by atherosclerosis. This study examined the effect of a plant-based diet (PBD) on vascular function in PAD patients.METHODs: Patients with PaD were randomized to plant-based dietary intervention (PBD group, n = 24) or no specific dietary advice (control group, n = 28). Biochemical parameters, including lipid profile and inflammatory biomarkers, and nitric oxide were measured at baseline and 4 months after dietary intervention. Vascular function including brachial artery flow-mediated vasodilation (FMD), carotid intima-media thickness(IMT), carotid-femoral pulse wave velocity (PWV), and brachial-ankle PWV were measured at baseline and 4 months after dietary intervention.RESULTS: Biochemical parameters were similar at baseline between the 2 groups. There was no change in any of the biochemical parameters in the control group at 4 months. However, patients in the PBD group had a significant improvement in lipid profile, including total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein a1 (APO-A1) levels. Greater nitric oxide and reduced high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were found in the PBD group at 4 months, whereas there were no changes in the control group. at baseline, FMD was similar between the 2 groups. after 4 months, PBD participants showed significant endothelial function improvement in FMD response and arterial stiffness response, with increased carotid-femoral and brachial-ankle PWV compared to the control group.&#x0D; CONCLUSIONS: A plant-based diet improves vascular endothelial function in PaD patients following 4 months of dietary intervention. This dietary intervention can result in decreased serum cholesterol and inflammatory biomarkers, which may further enhance vascular endothelial function.&#x0D; KEYWORDS: Plant-based diet; Vascular endothelial function; Flow-mediated dilation; Brachial artery reactivity test

Xanthine oxidoreductase activity correlates with vascular endothelial dysfunction in patients with type 1 diabetes.

Xanthine oxidoreductase (XOR) is an enzyme regulating uric acid synthesis and generation of reactive oxygen species. Several studies suggested relationship between XOR and atherosclerotic diseases; however, few previous studies have directly examined the relationship between XOR and vascular endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the relationship between XOR activity and vascular endothelial function in patients with T1DM. Seventy-one patients with T1DM participated in the study and underwent assessments, including plasma XOR activity and flow-mediated dilation (FMD), to measure vascular endothelial function. The natural logarithm value of XOR activity (ln-XOR) was 3.03 ± 0.99pmol/h/mL, and FMD was 5.5% ± 2.4%. FMD was inversely and significantly correlated with ln-XOR (correlation coefficient: r = - 0.396, P < 0.001), UA (r = - 0.252, P = 0.034), and asymmetric dimethylarginine (ADMA) (r = - 0.414, P < 0.001). ln-XOR showed positive correlation with HbA1c (r = 0.292, P = 0.013), ALT (r = 0.658, P < 0.001), and ADMA (r = 0.363, P = 0.002). Stepwise multiple regression analysis showed that ln-XOR (standard partial regression coefficient: β = - 0.254, P = 0.018) was an independent explanatory variable of FMD. The results of this study showed for the first time that XOR activity is associated with glycemic control in patients with T1DM and that XOR activity is associated with vascular endothelial dysfunction.

Application of non-invasive detection of peripheral vascular dysfunction in ovarian hyperstimulation syndrome (OHSS): A pilot study of clinical relevance

ObjectiveThe current study tested the hypothesis that vascular endothelial function, as reflected by the reactive hyperemia index (RHI), and biochemical factors, including VEGF, TNFα, CRP, inhibin A, and inhibin B, were involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Materials and methodsThis study was conducted between June 2010 and June 2012, enrolling 15 patients with OHSS and 6 healthy control subjects <45 years of age. Detailed clinical parameters were reviewed, including serum VEGF, TNFα, CRP, inhibin A, inhibin B, and hematocrit. RHI assessed by novel automatic peripheral arterial tonography was used to evaluate the vascular endothelial function. ResultsTwenty-one subjects were evaluated. There was no significant difference between patients with OHSS and control subjects with respect to VEGF, TNFα, CRP, inhibin A and inhibin B. The RHI was not significantly different between patients with OHSS and control subjects (mean, 1.8 ± 0.4 vs. 1.7 ± 0.2). The hematocrit was significantly different between patients with OHSS and control subjects. ConclusionsOur preliminary data did not reveal direct evidence of vascular endothelial dysfunction in patients with OHSS. To identify whether RHI could reflect vascular endothelial dysfunction in patients with OHSS, more cases with different severities of OHSS should be recruited in the future study.

Restless legs syndrome is associated with arterial stiffness and clinical outcome in stroke patients

ObjectiveRestless legs syndrome (RLS) has been associated with vascular diseases, including cerebrovascular and cardiovascular diseases. Among the various mechanisms in RLS, peripheral vascular endothelial dysfunction in patients with RLS has recently been proposed as a vascular pathophysiology of RLS. This study investigated arterial stiffness related to RLS in acute ischemic stroke patients and its influence on stroke outcome. MethodsRLS in patients with acute ischemic stroke was assessed based on the four essential criteria of the International Restless Legs Syndrome Study Group described in 2003. The patients’ clinical and laboratory characteristics, arterial stiffness, small vessel disease occurrence, and burden on brain MRI were recorded. Stroke severity was determined using the National Institute of Health Stroke Scale (NIHSS), and clinical outcomes were determined using the modified Rankin Scale. ResultsOf 296 patients with acute ischemic stroke, 16 (5.4%) were diagnosed with restless legs syndrome. Logistic regression analysis showed that a 1 m/s increase in brachial arterial pulse wave velocity was associated with the diagnosis of RLS (odds ratio, 1.092; 95% confidence interval, 1.019–1.170, p = 0.012). Diagnosis of RLS in patients with acute ischemic stroke was associated with poor clinical outcome three months after stroke (modified Rankin Scale 3–6) (odds ratio, 4.263; 95% confidence interval, 1.229–14.792, p = 0.022) along with initial NIHSS score. ConclusionRLS in patients with acute ischemic stroke is associated with increased arterial stiffness and poor clinical outcomes.

Hyperbaric oxygen may improve vascular endothelial function in patients undergoing coronary stent implantation

Hyperbaric oxygen (HBO2) therapy improves myocardial function and reduces clinical restenosis in coronary arteries. This study aims to evaluate whether the HBO2 therapy can improve vascular endothelial dysfunction in patients undergoing coronary stent implantation. The retrospective study included 115 patients undergoing coronary stent implantation. Patients receiving HBO2 therapy were included in the HBO2 group (n=55) and those without HBO2 therapy were included as controls (n=60). The levels of brachial artery endothelial-dependent flow-mediated dilation (FMD), endothelial-independent nitrate-mediated dilatation (NMD), nitric oxide (NO), endothelin-1(ET-1), calcitonin gene-related peptide (CGRP) and high-sensitivity C-reactive protein (hs-CRP) were used to evaluate vascular endothelial function. There were no significant differences with regard to the above parameters at baseline in either group (p⟩0.05). In both the HBO2 and control groups the levels of FMD, NO and CGRP after treatment were significantly higher than those before treatment (p⟨0.05). The levels of hs-CRP and ET-1 after treatment were significantly lower than those before treatment (p⟨0.05). After treatment, the levels of FMD, NO and CGRP in the HBO2 group were significantly higher than those of the control group (p⟨0.05), whereas the hs-CRP and ET-1 levels were significantly lower than those of the control group (p⟨0.05). Using HBO2 therapy as an adjunct treatment in patients undergoing coronary stent implantation may significantly improve vascular endothelial function. HBO2 therapy may have the potential to alter the course of coronary artery disease in the future. Further randomized, multicenter, prospective studies are needed.

TNFRSF11B: A potential plasma biomarker for diagnosis of obstructive sleep apnea

BackgroundObstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. MethodsThe study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. ResultsOur data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). ConclusionsPlasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.

Periodontitis is associated with systemic inflammation and vascular endothelial dysfunction in patients with lacunar infarct.

Periodontitis has been associated with lacunar infarct (LI), a type of cerebral small vessel disease. The objective of this study was to ascertain whether periodontitis is associated with increased circulating levels of systemic inflammation and endothelial dysfunction biomarkers in patients with LI. One hundred twenty patients with LI and 120 healthy controls underwent a full-mouth periodontal examination. The periodontal inflamed surface area (PISA) was calculated for each participant. Demographic, medical, and neurological information were recorded from all of them. In addition, blood samples were collected in order to investigate differences in terms of interleukin (IL)-6, IL-10, pentraxin (PTX) 3, soluble fragment of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and amyloid-beta (Aβ) peptides (i.e., Aβ1-40 , and Aβ1-42 ) measured in serum. Periodontitis was independently associated with increased levels of IL-6 (R2 =0.656, P<0.001), PTX3 (R2 =0.115, P<0.001), sTWEAK (R2 =0.527, P<0.001), and Aβ1-40 (R2 =0.467, P<0.001) in patients with LI. Within patients with poor outcome, PISA positively correlated with IL-6 (r=0.738, P<0.001), PTX3 (r=0.468, P=0.008), sTWEAK (r=0.771, P<0.001), and Aβ1-40 (r=0.745, P<0.001). Our data suggest a link between periodontitis, systemic inflammatory response, and disruption of the vascular endothelial function in patients with LI. Experimental studies are needed to elucidate possible pathways through which periodontitis could lead to this systemic inflammatory state with impairment of the endothelial function in LI. Further longitudinal studies with large samples are warranted to confirm our findings.