Vascular Cellular Adhesion Molecule-1 Research Articles

Adiponectin accumulation in the retinal vascular endothelium and its possible role in preventing early diabetic microvascular damage

Adiponectin (APN), a protein abundantly secreted from adipocytes, has been reported to possess beneficial effects on cardiovascular diseases in association with its accumulation on target organs and cells by binding to T-cadherin. However, little is known about the role of APN in the development of diabetic microvascular complications, such as diabetic retinopathy (DR). Here we investigated the impact of APN on the progression of early retinal vascular damage using a streptozotocin (STZ)-induced diabetic mouse model. Our immunofluorescence results clearly showed T-cadherin-dependent localization of APN in the vascular endothelium of retinal arterioles, which was progressively decreased during the course of diabetes. Such reduction of retinal APN accompanied the early features of DR, represented by increased vascular permeability, and was prevented by glucose-lowering therapy with dapagliflozin, a selective sodium-glucose co-transporter 2 inhibitor. In addition, APN deficiency resulted in severe vascular permeability under relatively short-term hyperglycemia, together with a significant increase in vascular cellular adhesion molecule-1 (VCAM-1) and a reduction in claudin-5 in the retinal endothelium. The present study demonstrated a possible protective role of APN against the development of DR.

Abstract P086: Endothelial Dysfunction Markers And Incident Chronic Kidney Disease In The Regards Cohort

Background: Much of chronic kidney disease (CKD) is unexplained by traditional risk factors. Endothelial dysfunction is highly prevalent in CKD and may be a potential target for reducing CKD incidence or progression. We sought to determine the association of plasma biomarkers of endothelial dysfunction with incident CKD in a large prospective cohort. Methods: REGARDS is a prospective population-based cohort of 30,239 Black and White US adults aged ≥45. Baseline biomarkers of endothelial dysfunction (plasma factor VIII, E-selectin, intercellular cellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1)) were measured in individuals without CKD who attended a second visit a median of 9.4 years after baseline. Incident CKD was defined as eGFR <60 ml/min/1.73m 2 and a decline of 40%. We used sequential logistic regression models adjusted for confounders to assess associations and tested for interactions by each of age, sex, race, and diabetes. Results: After exclusions, we studied 3,300 participants (median age 62, 49% women, 46% Black, 50% hypertensive, 15% diabetic). 228 (6.9%) developed CKD by the second visit. Substantial interactions were observed for several markers, so stratified analyses were presented (Table). In minimally adjusted models, independent positive associations with CKD were seen with higher levels of each marker: factor VIII in White non-diabetics, E-selectin in women <65 years, ICAM-1 in all participants, and VCAM-1 in White men and women (Table). Final adjustment attenuated associations in some groups, but not all. Among the above minimally adjusted results, all associations remained independent after final adjustment except models for VCAM-1; trends for increased CKD with higher VCAM-1 were apparent in White women and Black men, but these were not statistically significant. Conclusion: Several plasma markers of endothelial dysfunction were highly relevant to CKD incidence in important subgroups, which may reveal insights into reducing the burden of CKD.

Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice.

Adhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However, its role in angiotensin (Ang) II -induced hypertension and vascular dysfunction remains largely unknown. Wild-type (WT) mice were administered a VCAM-1 neutralizing antibody (0.1 or 0.2 mg/mouse/day) or IgG control and then infused with Ang II (490 ng kg−1 min−1) or saline continuously for 14 days. Systolic blood pressure (SBP) was measured with a tail-cuff system, pathological changes in the aorta were assessed by histological staining, and vascular relaxation was analyzed an aortic ring assay. Our results indicated that compared with saline infusion, Ang II infusion significantly upregulated VCAM-1 expression in the mouse aorta and serum. Moreover, Ang II infusion markedly increased arterial hypertension, wall thickness, fibrosis, infiltration of Mac-2+ macrophages, reactive oxygen species (ROS) production and vascular relaxation dysfunction. Conversely, blockade of VCAM-1 with a neutralizing antibody substantially alleviated these effects. In vitro experiments further confirmed that the VCAM-1 neutralizing antibody inhibited Ang II-induced macrophage adhesion and migration and DNA damage and oxidative stress in endothelial cells (ECs). In conclusion, these results indicate that blockade of VCAM-1 exerts a protective effect against Ang II-induced arterial hypertension and dysfunction by regulating monocytes adhesion and infiltration into the endothelium and represents a novel therapeutic approach for hypertension.

Rotigotine protects against oxidized low-density lipoprotein(ox-LDL)-induced damages in human umbilical vein endothelial cells(HUVECs)

ABSTRACT Rotigotine is a non-ergoline dopamine agonist that has been licensed for the treatment of Parkinson’s disease. Cardiovascular diseases are the world’s leading cause of death. Ox-LDL- induced endothelial damages are involved in the initiation and progression of cardiovascular diseases. In this study, we assessed the beneficial properties of Rotigotine on ox-LDL-induced insults to HUVECs to highlight its potential use in the treatment of cardiovascular diseases. Our findings show that Rotigotine suppresses the expressions of low-density lipoprotein receptor (LDL-R), proprotein convertase subtilisin/kexin type 9 (PCSK-9), and sterol regulatory element-binding protein (SREBP-2). It also inhibits ox-LDL-induced cholesterol accumulation in endothelial cells (ECs), improves U937 monocytes adhesion, and decreases the representation of NADPH oxidase (NOX-4) and generation of reactive oxygen species (ROS) in endothelial cells (ECs). Furthermore, Rotigotine inhibited the expressions of both vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs and had anti-inflammatory efficacy in ox-LDL-induced cells by inhibiting the expressions of pro-inflammatory cytokines. Notably, Rotigotine inhibits the activation of nuclear factor-kappaB (NF-κB) by preventing nuclear translocation of NF-κB p65 and reducing the luciferase activity of NF-κB reporter. We, therefore, conclude that these effects of Rotigotine on HUVECs suggest that it may play a therapeutic role in cardiovascular diseases.

Pinitol Protects Against Ox-Low-Density Lipoprotein-Induced Endothelial Inflammation and Monocytes Attachment.

Atherosclerosis is a cardiovascular disease that affects a majority of people around the world at old age. Atherosclerosis is slow to develop and challenging to treat. Endothelial dysfunction caused by oxidative stress, inflammation, and other pathological factors drives the process of atherogenesis. LOX-1 is one of the main scavenging receptors for oxidized low-density lipoprotein (ox-LDL) and contributes to atherogenesis by inducing overproduction of reactive oxygen species, increased expression of proinflammatory cytokines, and secretion of cellular adhesion molecules. In addition, activation of LOX-1 inhibits the expression of KLF2, a key protective factor against atherosclerosis. In this study, we investigated the effects of pinitol, and naturally occurring cyclic polyol, on endothelial dysfunction induced by ox-LDL. Our findings show that pinitol revealed a good safety profile, as evidenced by reducing lactate dehydrogenase release in human aortic endothelial cells. In our experiments, pinitol reduced the production of reactive oxygen species and expression of IL-6 and monocyte chemoattractant protein-1 induced by ox-LDL. Pinitol also significantly reduced the attachment of THP-1 monocytes to endothelial cells via downregulation of vascular cellular adhesion molecule-1 and E-selectin. Importantly, we found that pinitol reduced the expression of LOX-1 induced by ox-LDL and rescued the expression of KLF2, which is dependent on ERK5 expression. Together, our findings provide notable evidence that pinitol may have potential implication in the prevention and treatment of atherosclerosis.

Cardiovascular mortality and microinflammation in abdominal obese hemodialysis patients

Purpose: Abdominal adipose tissue has important inflammatory properties and is a source of various inflammatory mediators. Given that concentrations of some inflammatory mediators are high among hemodialysis (HD) patients, abdominal obesity may play an important role in the pathogenesis of microinflammation which is known to be associated with accelerated atherosclerosis. The aim of our study was to determine the impact of microinflammation on cardiovascular (CV) mortality in abdominal obese HD patients.
 Methods: Seventy–one HD patients (mean age 59.3 ± 12.8 years) were included in our study. Waist circumference (WAC) was measured and abdominal obesity was defined according to the International Diabetes Federation. Serum levels of lipids (triglycerides, high density lipoproteins (HDL) cholesterol, low density lipoproteins (LDL) cholesterol) and inflammatory mediators (interleukin–6, tumor necrosis factor–alpha, vascular cellular adhesion molecule–1 (VCAM–1), intercellular adhesion molecule–1 (ICAM–1)) were measured. Patients were observed from the date of measurement (November 2003) of inflammatory mediators until their death or to 10th of November 2009.
 Results: The mean WAC value for men was 97.6 ± 16.1 cm, and for women 92.2 ± 15.9 cm. Abdominal obesity was found in 62% of the enrolled patients. Cox regression analysis showed that the inflammatory mediators VCAM–1 (p<0.031) and ICAM–1 (p<0.024) were predictors of CV mortality in abdominal obese HD patients. Both inflammatory mediators remained predictors of CV mortality if age and other known risk factors for atherosclerosis (arterial hypertension, smoking, HDL and LDL cholesterol and triglycerides) were included in the analysis.
 Conclusion: The results of our study indicate that microinflammation is associated with CV mortality in abdominal obese HD patients.

Immune-inflammatory, coagulation, adhesion, and imaging biomarkers combined in machine learning models improve the prediction of death 1year after ischemic stroke.

Some clinical, imaging, and laboratory biomarkers have been identified as predictors of prognosis of acute ischemic stroke (IS). The aim of this study was to evaluate the prognostic validity of a combination of clinical, imaging, and laboratory biomarkers in predicting 1-year mortality of IS. We evaluated 103 patients with IS within 24h of their hospital admission and assessed demographic data, IS severity using the National Institutes of Health Stroke Scale (NIHSS), carotid intima-media thickness (cIMT), and degree of stenosis, as well as laboratory variables including immune-inflammatory, coagulation, and endothelial dysfunction biomarkers. The IS patients were categorized as survivors and non-survivors 1year after admission. Non-survivors showed higher NIHSS and cIMT values, lower antithrombin, Protein C, platelet counts, and albumin, and higher Factor VIII, von Willebrand Factor (vWF), white blood cells, tumor necrosis factor (TNF)-α, interleukin (IL)-10, high-sensitivity C-reactive protein (hsCRP), and vascular cellular adhesion molecule 1 (VCAM-1) than survivors. Neural network models separated non-survivors from survivors using NIHSS, cIMT, age, IL-6, TNF-α, hsCRP, Protein C, Protein S, vWF, and platelet endothelial cell adhesion molecule 1 (PECAM-1) with an area under the receiving operating characteristics curve (AUC/ROC) of 0.975, cross-validated accuracy of 93.3%, sensitivity of 100% and specificity of 85.7%. In conclusion, imaging, immune-inflammatory, and coagulation biomarkers add predictive information to the NIHSS clinical score and these biomarkers in combination may act as predictors of 1-year mortality after IS. An early prediction of IS outcome is important for personalized therapeutic strategies that may improve the outcome of IS.

The dynamic of Soluble Vascular Cellular Adhesion Molecule -1 (sVCAM-1) level in Overnutritious children with Dengue Infection

Introduction: Dengue infection is still posed a significant medical challenge for pediatric population in developing countries. However, increased prevalence of overweight and obesity among children in those countries increased the possibility of the coexistence of these conditions. However, their interaction is still under investigated. Therefore, this study was aimed to study the dynamic of sVCAM-1 level as the known predictor of the severity of dengue infection with over nutritional status in children with dengue infection.Method: An analytic observational nested case-control study was conducted in Paediatric Division Sanglah General Hospital, Bali. The children with DHF between 6 months old to 12 years old were included as the case group while control groups consisted of pediatric patients with just Dengue Fever (DF) with the same age range. The diagnosis of dengue was established using 1997 WHO criteria while nutritional status was assessed using WHO curve. The sVCAM-1 was evaluated using ELISA technique.Results: The level of sVCAM-1 was significantly higher in patients with DHF than patients with DF only. The level was also fluctuated more in DHF patients. Likewise, the sVCAM-1 level was also significantly higher in DHF patients with overnutrition compared to normal DHF patients with a more fluctuated pattern over the course of 3 days (starting from day 4 to day 7). Finally, no significant finding was observed in sVCAM-1 level in DSS patients albeit the difference in concentration pattern.Conclusion: Overnutrition is seems to be associated with higher concentration of sVCAM-1 and higher fluctuation of its concentration in children with DHF.

A lower admission level of interleukin-6 is associated with first-pass effect in ischemic stroke patients

BackgroundFirst-pass effect (FPE) defined as a complete or near-complete reperfusion achieved after a single thrombectomy pass is predictive of favorable outcome in acute ischemic stroke (AIS) patients. We aimed to...

Activation of GPR30 with G1 inhibits oscillatory shear stress-induced adhesion of THP-1 monocytes to HAECs by increasing KLF2.

Atherosclerosis is a chronic inflammatory disease known to be mediated by numerous factors, among which endothelial dysfunction plays a critical role. Oscillatory shear stress induces endothelial cells to lose their anti-atherosclerotic properties and downregulates the expression of the innate protective transcription factor, Krüppel-like factor 2 (KLF2), which is typically upregulated in vascular endothelial cells in response to harmful stimuli. Oxidative stress and inflammation impair endothelial function and damage their survival. Oscillatory shear stress also promotes generation of reactive oxygen species and production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), thereby further promoting endothelial dysfunction and formation of atherosclerotic plaque. A major event in the development of atherosclerotic plaque is rolling and adhesion of monocytes to endothelial cells, which is mediated by adhesion molecules including vascular cellular adhesion molecule 1 and endothelial-selectin. Expression of these molecules is also upregulated by oscillatory shear stress. Estrogen has long been recognized as a protective agent against atherosclerosis, but the mechanisms through which estrogen receptors prevent atherogenesis remain unclear. In the present study, we investigated the role of the G-coupled protein estrogen receptor (GPR30) in oscillatory shear stress- induced endothelial dysfunction. We show that agonism of GPR30 by its specific agonist G1 prevented oscillatory shear stress -induced oxidative stress markers and production of inflammatory cytokines and adhesion molecules. As a result, GPR30 activation suppresses monocytes adhesion to endothelial cells. Furthermore, we demonstrate that GPR30 prevents oscillatory shear stress- induced downregulation of KLF2 via ERK5 pathway. These findings suggest that endothelial GPR30 is potential target to suppress oscillatory shear stress mediated atherogenesis.

Abstract P768: Vascular Cellular Adhesion Molecule Targeting for the Treatment of Acute Neurovascular Inflammation

Targeted drug delivery is an attractive strategy for treatment of life-threatening inflammatory brain pathologies such as ischemic stroke. In these conditions, adhesion molecule expression (e.g. vascular cellular adhesion molecule-1, VCAM) is upregulated on endothelium. Hence, VCAM represents a relevant target for selective drug delivery. We have utilized αVCAM monoclonal antibodies to target therapeutic proteins and nanocarriers (liposomes and lipid nanoparticles, LNPs) to the pathologically-altered vasculature.To assess tissue biodistribution and therapeutic effects of VCAM-targeted agents, we used 2 mouse models: 1) acute inflammation induced by intra-striatal injection of tumor necrosis factor-α (TNF), and 2) ischemic stroke induced by transient middle cerebral artery occlusion (tMCAO). Biodistribution was assayed by measuring radioactivity in blood and organs 30 minutes after injection. Efficacy was determined by tracing radiolabeled albumin extravasation to assess edema.The results showed that VCAM targeting was increased by TNF injection, and that targeting to VCAM enhanced the cerebral accumulation of αVCAM conjugated thrombomodulin (TM) and nanocarriers by orders of magnitude (Fig A). It is noteworthy that αVCAM-TM and free αVCAM antibody had similar levels of brain uptake. Our data also demonstrated the protective effect of αVCAM-liposome loaded with dexamethasone on brain edema (Fig B), indicating the therapeutic potential of VCAM-targeting drug delivery strategies. Further, the results in tMCAO model recapitulated our findings in the TNF model that targeting to VCAM significantly improves delivery to the ischemic brain (Fig C). In summary, we have shown that targeting VCAM permits delivery of a diverse array of therapeutics to the inflamed vasculature in conditions such as ischemic stroke. Future work will focus on evaluating the therapeutic properties of VCAM-targeted drug delivery strategies.

Vedolizumab for the Treatment of Noninflammatory Bowel Disease Related Enteropathy

Vedolizumab has become an integral part of the therapeutic armamentarium for patients with inflammatory bowel disease (IBD) who have failed conventional medical therapy. Vedolizumab is an α4β7 integrin antagonist that inhibits intestinal T-cell translocation by blocking integrin interactions with mucosal vascular addressin cellular adhesion molecule 1, reducing lymphocyte-mediated inflammation.1 Its gut selective mode of action and favorable safety profile have led to reports of off-label use for non-IBD-related inflammatory intestinal disorders, such as microscopic colitis,2 and small intestinal inflammatory conditions including autoimmune enteropathy3 and common variable immune deficiency-related enteritis.4 Treatment of non-IBD-related enteropathies is challenging with no approved therapies or established treatment algorithms. We conducted a literature review to assess clinical, endoscopic, and histologic improvement in patients treated with vedolizumab for non-IBD enteropathies refractory to conventional therapy.

Endothelial Activation and Immune Thrombocytopenia: An Engagement Waiting for Consolidation.

Immune thrombocytopenia (ITP) appears to be a heterogeneous disease. In some patients, autoimmunity may be associated with an inflammatory process, and in other patients, low platelets may interfere with other aspects of the coagulation system. Either may predispose to thrombosis or bleeding. Further investigation of the interactions of platelets, with inflammatory cytokines and endothelial biomarkers, may help us to better understand the disease, and to recognize those patients at risk of bleeding, or conversely thrombosis. The aim of this work is to estimate von Willebrand factor (vWF) and vascular cellular adhesion molecule (V-CAM) serum levels in adult immune thrombocytopenic patients (ITP) and to decipher their possible clinical correlates. Eighty adults (≥ 18 years) were enrolled in the study; naive newly diagnosed 40 patients with primary ITP (according to the ASH 2019) and 40 sex and age-matched healthy controls, all groups are subjected for complete blood count (CBC), liver, and renal function tests, ESR, CRP, V-CAM, and VWF-Ag by enzyme-linked immunosorbent assay (ELISA). There was a highly statistically significant difference between case and control as regards to the mean level of VWF-Ag and V-CAM. vWF and V-CAM could serve as biomarkers for endothelial alterations and should be investigated as a predictor of thrombocytopenic bleeding and tailor patient management accordingly.

The effect of barberry (Berberis vulgaris) consumption on flow-mediated dilation and inflammatory biomarkers in patients with hypertension: A randomized controlled trial.

Hypertension is considered as an important cardiovascular risk factor and evidence suggests that hypertension and endothelial dysfunction reinforce each other. Polyphenol-rich foods, such as barberry can reduce the risk of cardiovascular disease. Our aim was to investigate the effects of barberry consumption on vascular function and inflammatory markers in hypertensive subject. In this randomized controlled parallel trial, 84 hypertensive subjects of both genders (aged 54.06 ± 10.19 years; body mass index 28.02 ± 2.18 kg/m2 ) were randomly allocated to consume barberry (10 g/day dried barberry) or placebo for 8 weeks. Before and after the intervention, changes in brachial flow-mediated dilation (FMD) and plasma macrophage/monocyte chemo-attractant protein-1 (MCP-1), vascular cellular adhesion molecule-1, and intracellular adhesion molecule-1 (ICAM-1) were measured. An intention-to-treat analysis was performed. Compared to placebo (n = 42), barberry consumption (n = 42) improved FMD (B [95% CI] was 6.54% [4.39, 8.70]; p < .001) and decreased plasma ICAM-1 (B [95% CI] was -1.61 ng/ml [-2.74, -0.48]; p = .006). MCP-1 was significantly lower in the barberry group compared with the placebo group (B [95% CI] was -37.62 pg/ml [-72.07, -3.17]; p = .033). Our results indicate that barberry consumption improves FMD and has a beneficial effect on plasma ICAM-1 and MCP-1 in hypertensive patients. This trial was registered at the Iranian Registry of Clinical Trial (IRCT) with number IRCT20160702028742N8.

Effect of Rosuvastatin Therapy on Biomarkers of Inflammation and Immune Activation in People With Human Immunodeficiency Virus at Intermediate Cardiovascular Risk.

Statins may help prevent cardiovascular disease (CVD) in people with human immunodeficiency virus (PWH) with chronic inflammation owing to their pleotropic lipid-lowering and anti-inflammatory properties. The impact of 48 weeks of rosuvastatin therapy on inflammation and immune activation in a double-blind, placebo-controlled trial in PWH at moderate cardiovascular disease risk was assessed. Rosuvastatin did not alter plasma levels of interleukin 6, soluble tumor necrosis factor receptor type 2, CXCL10, soluble CD14, or soluble vascular cellular adhesion molecule 1 (P ≥ .1 for all). Proportions of CD16+ monocyte subsets were increased in PWH receiving rosuvastatin. The potential benefits of statin use in PWH with normal lipid levels requires further clinical outcome research.

Fecal Calprotectin Is Elevated in HIV and Related to Systemic Inflammation.

Fecal calprotectin (FC), a biomarker of gastrointestinal (GI) inflammation, is used in the diagnosis and management of inflammatory bowel disease. HIV infection severely damages gut-associated lymphoid and epithelial tissues leading to GI inflammation that drives systemic inflammation and increases subsequent risk of comorbidities. For the first time, we compared FC concentrations by HIV and antiretroviral therapy (ART) status and determined the relationship to systemic inflammation. People with and without HIV were enrolled and underwent a comprehensive clinical and laboratory assessment. Stool samples were collected, and FC was measured by enzyme-linked immunosorbent assay ELISA. Plasma biomarkers of inflammation were also measured. One hundred one participants with HIV (83 ART-treated and 18 ART-naive) and 89 uninfected controls were enrolled. There were no significant differences between ART-naive and ART-treated participants, but both HIV groups had significantly higher FC concentrations than controls when FC was considered as a continuous variable or by cut-offs used in inflammatory bowel disease. The highest median and largest proportion of participants with FC >100 µg/g were seen in ART-naive, followed by ART-treated and then controls. Among HIV participants, FC concentrations were positively associated with high-sensitivity C-reactive protein, soluble tumor necrosis factor receptor II, and soluble vascular cellular adhesion molecule and inversely associated with CD4 counts. FC concentrations are elevated in HIV regardless of ART status. ART and immune reconstitution seem to reduce FC but not to concentrations seen in uninfected controls. Our results suggest a role for FC as a noninvasive surrogate measurement of GI inflammation and associated systemic inflammation in HIV.

Associations of Sedentary Patterns with Cardiometabolic Biomarkers in Physically Active Young Males.

ABSTRACTPurposeSitting time (ST) is a serious global health issue and positively associated with cardiometabolic disease. The present study investigated associations between objectively measured ST, sedentary patterns, and cardiometabolic biomarkers in physically active young males.MethodsCross-sectional analysis was completed in 94 males 18–35 yr of age. Total ST, prolonged sedentary bouts (≥30 min with no interruption), and sedentary breaks (transitions from sitting/lying to standing/stepping) were assessed using activPAL. Lipids, insulin, C-peptide, C-reactive protein (CRP), vascular cellular adhesion molecule-1, intercellular adhesion molecule 1, E-selectin, P-selectin, leptin, resistin, and adiponectin were measured using assay kits. The expression of specific proteins related to endothelial dysfunction was determined using quantitative real-time polymerase chain reaction. Associations between total ST, prolonged sedentary bouts, and sedentary breaks with cardiometabolic biomarkers and total ST and levels of gene expression were assessed using generalized linear models.ResultsTotal ST was significantly associated with triglycerides (B = 1.814), insulin (B = 2.117), homeostasis model assessment of insulin resistance (B = 0.071), and E-selectin (B = 2.052). Leptin (B = 0.086), E-selectin (B = 1.623), and P-selectin (B = 2.519) were significantly associated with prolonged sedentary bouts, whereas leptin (B = −0.017) and CRP (B = −0.016) were associated with sedentary breaks. After adjustment for moderate to vigorous physical activity, the associations between triglycerides (B = 2.048) and total ST, and between CRP (B = −0.016) and sedentary breaks, remained significant. E-selectin mRNA levels (B = 0.0002) were positively associated with ST with or without adjustment for moderate to vigorous physical activity.ConclusionsTotal ST and prolonged sedentary bouts were positively associated with several cardiometabolic biomarkers, with interruptions in ST potentially contributing to reduced cardiometabolic risk in physically active young male adults.

Associations Of Objectively Measured Sedentary Time With Endothelial Function Biomarkers In Young Male Adults

PURPOSE: Sedentary behavior (SB) is recognized as a serious global health issue. SB-induced down regulation of shear rate and blood flow play a key role in the pathogenesis of endothelial dysfunction, an important prognostic marker for cardiovascular disease. The purpose of this study was to assess the association between objectively measured sedentary time and endothelial function biomarkers in young male adults. METHODS: A total of 93 participants (age, 21.8 ± 3.8 yr; body height, 171.6 ± 6.4 cm; body weight, 62.1 ± 6.4 kg; % body fat, 15.6 ± 4.6%; body mass index (BMI) 21.1 ± 1.7 kg/m2; waist circumference 74.5 ± 5.1 cm; heart rate (HR) 67.6 ± 9.5 bpm; systolic blood pressure (SBP) 108.4 ± 9.1 mmHg; diastolic blood pressure (DBP) 71.6 ± 8.1 mmHg) wore the activPALTM continuously for 7 days without removal. Total sedentary time was assessed using PALanalysis v8.0. Bedtime and wake-up time were recorded by participants. Sleep duration was determined as the time between bed time and wake-up time. Sedentary time during waking hours was calculated as the total sitting/lying time minus sleep duration. A fasting venous blood sample was drawn from each of the participants from which serum endothelial cell adhesion molecules E-selection, P-selectin, Intercellular Adhesion Molecule 1 (ICAM-1) and Vascular Cellular Adhesion Molecule 1 (VCAM-1) were measured using flow cytometry. Multiple linear regression models examined the associations of sedentary time with endothelial function biomarkers using SPSS version 23.0. RESULTS: E-selectin (β = 0.226, 95% confidence interval [CI]: 0.021, 0.431) and P-selectin (β = 0.216, 95% CI:0.017, 0.415) were positively associated with sedentary time after controlling for age and BMI. After moderate-to -vigorous physical activity (MVPA) was added to the model, there were no significant association between E-selectin and sedentary time. No significant associations were found between ICAM-1 or VCAM-1 with sedentary time or between ICAM-1 or VCAM-1 with sedentary time after controlling age, BMI, and MVPA. CONCLUSIONS: Objectively measured sedentary time was positively associated with E-selectin and P-selectin in young male adults independent of age and BMI. MVPA may alleviate the adverse effects of sedentary time on biomarkers of endothelial function.

Endothelial dysfunction in HIV-positive patients with acute coronary syndromes

This study investigated endothelial function in HIV-positive patients with acute coronary syndrome (ACS). Flow-mediated dilatation, pulse-wave velocity, carotid intima-media thickness and endothelial biomarkers were used to non-invasively investigate endothelial dysfunction. Twenty HIV-positive patients with ACS (HIV+/ACS) were compared to 20 HIV-negative patients with ACS (HIV-/ACS) and 20 HIV-positive patients without ACS (HIV+/no ACS). Endothelial function measured by flow-mediated dilatation (FMD) was similar in both the HIV+/ACS (5.2; IQR 1.4-13.4%) and HIV-/ACS groups (3.7; IQR 2.3-4.4%) (p = 0.78). Arterial stiffness, measured by pulse-wave velocity (PWV) was low in all three cohorts. Carotid intima-media thickness (CIMT) was also low in all three cohorts. The vascular cellular adhesion molecule-1 (VCAM-1) levels in HIV-positive patients with and without ACS were significantly higher than in the HIV-/ACS cohort (p = 0.033 and 0.024, respectively). Non-invasive investigations such as FMD, CIMT and PWV did not identify patients with HIV who were at high risk of ACS. Endothelial biomarkers may be more useful markers to identify HIV-positive patients who have endothelial dysfunction and increased risk of ACS.

Blood pressure and its circadian pattern in obese and lean premenopausal women

Background. Obesity is frequently referred to as an independent risk factor for high blood pressure and hypertension is very prevalent among obese people. The aims of this study were: to compare office-based and 24 h blood pressure (BP) and its circadian pattern between lean and obese women; to study correlations between BP, insulin resistance (IR) and markers of subclinical inflammation/early atherosclerosis. Material and methods. Eighty-eight lean and 107 otherwise healthy obese women were characterized for anthropometrics, BP (office-based determinations and 24 h ABPM) and for glucose, insulin, triglycerides, inteleukin 6 (IL-6), tumor necrosis factor alpha (TNF-a), high-sensitivity C reactive protein (hs-CRP), retinol-binding protein 4 (RBP-4), leptin, adiponectin, resistin, monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular-cellular adhesion molecule 1 (VCAM-1). Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and McAuley indexes (also Matsuda in obese). Results. Obese group presented higher office-based systolic/diastolic BP, systolic ambulatory blood pressure monitoring (ABPM), and more non-dippers. HOMA-IR and body fat was correlated to systolic (r2 = 0.176) and glucose to diastolic (p = 0.008; r = 0.256) ABPM. Age, QUICKI, and TNF-a was correlated with dipping (r2 = 0.172); adiponectin, age, BMI, and glucose to systolic (r2 = 0.226) and diastolic (r2 = 0.215) office-based BP. Concerning lean women, MCP-1 was associated with diastolic ABPM (p = 0.013; r = 0.267). Systolic office-based BP was associated with waist-to-hip ratio (p = 0.01; r = 0.273); this and RBP-4 was correlated with office-based diastolic BP (r2 = 0.12). Conclusion. Although relatively healthy, obese women present higher BP than lean. Anthropometrics, IR, and fasting glucose all influence BP in obesity; additionally, IR is involved in non-dipping. No strong correlation exists between BP/dipping and subclinical inflammation in either group of women.