E-selectin Levels Research Articles

Pilot study of peripheral blood chemokines as biomarkers for atrial fibrillation-related thromboembolism and bleeding in elderly patients.

BackgroundThe scoring systems currently used to identify the potential for thrombosis and bleeding events in high-risk atrial fibrillation patients have certain limitations. The aim of this pilot study was to identify inflammatory chemokines with potential utility as sensitive biomarkers for the risk of thrombosis and bleeding in elderly patients with non-valvular atrial fibrillation.MethodsFrom January 1, 2014, to December 31, 2017, 200 consecutive elderly patients with atrial fibrillation (average age: 87.6 ± 7.7 years) were enrolled and followed up for 2 years to observe thromboembolic (arterial and venous) and bleeding events. Serum was collected upon enrollment, and the baseline levels of 27 chemokines were analyzed. During the 2-year follow-up, 12 patients were lost to follow-up. Among the 188 patients, there were 32 cases (17.0%) of AF-related thrombosis, 36 cases (19.1%) of arterial thrombosis, and 35 cases (18.6%) of major bleeding events.ResultsAmong 188 patients, 30 patients without clinical events (control group), 23 with arterial thrombosis, 15 with atrial fibrillation-related venous thromboembolism, and 12 with major bleeding were selected and randomly matched to compare chemokine levels. The baseline levels of interleukin-6, interleukin-10, vascular cell adhesion molecule-1, chemokine C-C-motif ligand, B-lymphocyte chemoattractant 1, interleukin-4, E-selectin, fractalkine, C-X-C motif chemokine 12, and granulocyte chemotactic protein 2 were found to differ statistically among the four groups (p < 0.05). Compared with that in the control group, the level of interleukin-4 in patients with atrial fibrillation-related thrombosis, arterial thrombosis, or major bleeding increased by 53-fold (0.53 vs. 0.01 pg/ml), 17-fold (0.17 vs. 0.01 pg/ml), and 19-fold (0.19 vs. 0.01 pg/ml), respectively. Compared with that in the control group, the level of interleukin-6 in patients with arterial thrombosis increased by six-fold (39.78 vs. 4.98 pg/ml).ConclusionsAmong elderly patients with atrial fibrillation at high risk of thromboembolism and bleeding, the baseline levels of interleukin-6, interleukin-4, and E-selectin were significantly increased in those that experienced thrombosis and bleeding events during the 2-year follow-up, indicating that these chemokines may serve as potential biomarkers for an increased risk of thrombosis and bleeding in this population.Clinical trial registration numberChiCTR-OCH-13003479.

Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression.

Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta.

Intrahepatic lipid content is independently associated with soluble E-selectin levels: The Maastricht study.

Evidence is accumulating that liver sinusoidal endothelial cells are involved in the pathogenesis of non-alcoholic fatty liver disease. Previous studies have suggested that the endothelial biomarker soluble E-selectin (sE-selectin) is to an important extent liver-derived. To study the relationship of intrahepatic lipid (IHL) content with sE-selectin at the population level. This study was conducted in participants of The Maastricht Study (n=1,634), a population-based cohort study enriched with patients with type 2 diabetes. We assessed the cross-sectional association between IHL content, quantified by MRI, and sE-selectin via multivariable regression with adjustment for age, sex, type 2 diabetes, educational level, BMI, Dutch Healthy Diet index, physical activity, and the Matsuda index. Standardized IHL content was associated with (log) sE-selectin (age-, sex- and type 2 diabetes-adjusted regression coefficient [B]: 0.048 [95%CI:0.038;0.058], p<0.001), even after full adjustment (B: 0.030 [0.019;0.042], p<0.001). Such an association was not observed for soluble vascular cell adhesion molecule 1 (sVCAM-1) levels. IHL content is an independent determinant of sE-selectin at the population level. These findings support further studies to unravel the involvement of liver sinusoidal endothelial cells in the different stages of non-alcoholic fatty liver disease and the specific role of E-selectin herein.

Assessment of Endothelial Dysfunction in Patients with Kawasaki Disease: A Meta-Analysis.

Kawasaki disease (KD) is a well-known systemic inflammatory vasculitis. Endothelial dysfunction is one of most easily overlooked non-coronary complications of KD. Several studies have assessed endothelial dysfunction using flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD), and biomarkers (E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1)). However, the results were inconsistent and incomplete. We searched five databases for eligible studies until March 8, 2022. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for FMD, NMD, and four biomarkers level between KD and healthy children. A meta-analysis with subgroup analysis was conducted. 40 studies with a total of 2670 children (1665 KD patients and 1005 healthy children) were identified. During the acute phase, KD patients had lower FMD compared to the control group (WMD = -10.39, 95% CI: -13.80- -6.98). During the subacute phase, KD patients had lower FMD compared to the control group (WMD = -15.07, 95% CI: -17.61- -12.52). During the convalescence phase, KD patients had lower FMD and similar NMD compared to the control group (WMD = -4.95, 95% CI: -6.32- -3.58; WMD = -0.92, 95% CI: -2.39-0.55, respectively). During the convalescence phase, those KD patients without coronary artery lesion (CAL), with CAL, even with coronary artery aneurysm, had progressively lower FMD compared to healthy children (WMD = -3.82, 95% CI: -7.30- -0.34; WMD = -6.32, 95% CI: -7.60- -5.04; and WMD = -6.97, 95% CI: -7.99- -5.95, respectively). Compared to KD patients without CAL, those with CAL had lower FMD (WMD = -1.65, 95% CI: -2.92- -0.37). KD patients had higher levels of E-selectin, P-selectin, and ICAM-1 compared to healthy controls during different phases. KD patients had a higher level of VCAM-1 compared to healthy controls only during the acute phase (WMD = 61.62, 95% CI: 21.38-101.86). Endothelial dysfunction is present since the onset of KD and persists for years, confirmed by the measurement of FMD and biomarkers from different phases. An assumption is advanced that FMD impairment (the severity of endothelial dysfunction) may be positively correlated with CAL severity during the convalescence phase.

Plasma E-selectin and kallistatin as predictive markers of histologic chorioamnionitis in women with preterm premature rupture of membranes.

We aimed to assess the predictive potential of 12 plasma biomarkers to predict acute histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM) and to develop multi-biomarker panels based on these biomarkers in combination with widely used conventional laboratory markers. This was a retrospective cohort study involving 81 singleton pregnant women (24-34weeks of gestation) who delivered within 96 h of blood sampling. White blood cell (WBC) count, differential counts, and C-reactive protein (CRP) levels were measured at admission. The levels of DKK-3, Fas, haptoglobin, IGFBP-2, kallistatin, MIP-1α, MMP-2, MMP-8, pentraxin 3, progranulin, E-selectin, and P-selectin were evaluated by ELISA using stored plasma samples. The primary outcome measure was acute HCA. Multivariate analyses showed that low plasma E-selectin and kallistatin levels were independently associated with HCA occurrence after adjusting for gestational age. Using a stepwise regression analysis, a multi-biomarker panel comprising plasma E-selectin, serum CRP, and WBC was developed, which provided a good prediction of acute HCA in women with PPROM (area under the curve [AUC], 0.899), with a significantly higher AUC than that of any single variable included in the panel (P<0.05). The plasma levels of DKK-3, Fas, haptoglobin, IGFBP-2, MIP-1α, MMP-2, MMP-8, pentraxin 3, and P-selectin were not significantly associated with HCA occurrence. This study identified E-selectin and kallistatin as potential plasma biomarkers associated with acute HCA in women with PPROM. Their combined analysis with serum CRP and WBC counts significantly improved acute HCA diagnosis.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study

BackgroundThere are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. MethodsThis was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. ResultsIncreasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). ConclusionsIncreased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

Wenyang Huazhuo Tongluo formula alleviates pulmonary vascular injury and downregulates HIF-1α in bleomycin-induced systemic sclerosis mouse model

BackgroundVascular damage, autoimmune abnormalities, and fibrosis are the three pathological features of systemic sclerosis (SSc).However, pulmonary vascular damage is the main factor affecting the progression and prognosis of SSc. The main purpose of this study was to explore the molecular mechanism of Wenyang Huazhuo Tongluo Formula in alleviating pulmonary vascular injury in bleomycin-induced SSc mouse model.MethodsMasson staining and H&E staining were used to analyze the degree of pulmonary vascular fibrosis and the infiltration of leukocyte cells in lung tissue ofbleomycin-induced SSc mouse models treated with saline (BLM group), Wenyang Huazhuo Tongluo Formula (WYHZTL group) and HIF-1α inhibitor KC7F2 (KC7F2 group). Blood vessel exudation was determined by analyzing the cell number and albumin concentration in bronchoalveolar lavage fluid using a cell counter and ELISA assay, respectively. The degree of vascular injury was assessed by measuring the expression levels of vWF, E-selectin, ICAM-1, VCAM-1, VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells using ELISA and immunofluorescence staining. Finally, the effect of Wenyang Huazhuo Tongluo Formula on the expression of HIF-1α was detected using immunofluorescence staining.ResultsWenyang Huazhuo Tongluo Formula and KC7F2 significantly inhibited bleomycin-induced pulmonary vascular fibrosis and the level of perivascular inflammatory cell infiltration. The number of cells and the concentration of albumin were significantly reduced in the bronchoalveolar lavage fluid of the WYHZTL group and KC7F2 group compared with the BLM group. In addition, treatment with Wenyang Huazhuo Tongluo Formula and KC7F2 significantly downregulated the expression levels of vWF, E-selectin, ICAM-1, VCAM-1 and HIF-1α, but upregulated the expression of VE-cadherin and claudin-5 in serum and pulmonary vascular endothelial cells, compared with treatment with saline.ConclusionsThis study reveals that Wenyang Huazhuo Tongluo Formula plays a new role in the treatment of SSc by alleviating pulmonary vascular damage. Furthermore, we found that Wenyang Huazhuo Tongluo Formula alleviates pulmonary vascular injury and inhibits HIF-1α expression.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

The Role of Endothelial Related Circulating Biomarkers in COVID-19. A Systematic Review and Meta-analysis.

Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity. We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWFAg), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported. A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05). Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.

Serum Chemerin and Apelin Levels in Obese Children: Relation to Endothelial Function and Inflammation from a Cross-sectional Case–Control Study

BACKGROUND: Childhood obesity is a global threat with subsequent health problems among which and most important is cardiovascular problems. It is now claimed that adipokines secreted by adipose tissue are responsible for such consequences. Newly discovered adipokines chemerin and apelin are under investigation for their link with obesity related co-morbidites. AIM: The aim of the present study was to assess the serum levels of chemerin and apelin in obese children and to explore the correlation between these two biomarkers and the inflammatory as well as the endothelial cell activation markers PATIENTS AND METHODS: This study was a cross-sectional case control study that comprised 45 pre-pubertal obese children aged (6– &lt; 12) years old of both sexes (22 males and 23 females), in addition to 45 matched age and sex lean children serving as controls (21 males and 24 females). Serum levels of chemerin, apelin, ICAM-1, E-selectin and hs-CRP were measured for obese and controls. RESULTS: Obese children showed higher levels of chemerin, apelin, ICAM-1 and E-selectin than controls. Chemerin and apelin showed significant correlations with all parameters except for age. Anthropometric parameters with hs-CRP revealed significant correlation even after adjustment for age and sex while apelin only showed a significant correlation with age. Multiple regression analyses with hs -CR , E-selectin and ICAM-1 as dependent variables and BMI Z score ,age, sex, chemerin and apelin as independent variables showed the effect of chemerin and apelin on the increased levels of hs -CR , E-selectin and ICAM-1 . CONCLUSION: Elevated levels of chemerin and apelin may serve as indices of ongoing obesity-related disorders in obese children.

Pathophysiology of metalloproteinase matrix in relation to morbid obesity and associated pathologies

Matrix Metalloproteinases (MMPs), these calcium-dependent zinc-containing endopeptidases play an important role in adipogenesis and angiogenesis by modifying tissues and degrading the extracellular matrix (ECM). Matrix glycoproteins, gelatin, collagens, proteoglycans and elastin are all found in the ECM. Current meta-analysis confirmed the lower levels of IL-6 and CRP was found following bariatric surgery. Several studies have shown correlations between E-selectin levels, BMI, and MMP-9 levels. There was also a strong link between the metalloproteinases MMP-2 and MMP-9. MMP-2 and adiponectin levels are related. MMP-9 levels, on the other hand, were modestly linked with E-selectin and HDL cholesterol levels, as previously stated. Also current observations imply that alterations in the ECM caused by MMP-mediated degradation may be crucial for the differentiation of adipocytes. The most crucial component of this is that MMPs are involved in the remodeling of tissue after gastric bypass surgery, as revealed by these markers (especially MMP-2 and MMP-9). Thus, it is tempting to assume that adipocyte derived MMPs may constitute a novel pharmaceutical target for limiting adipose tissue development through the reduction of adipocyte differentiation and angiogenesis. MMP-2 exhibits far more accurate oscillations than MMP-9 during pre- and post-surgical weight fluctuations, and hence may be used as a predictor for gastric bypass success. The purpose of this paper is to conduct a comprehensive review of the literature with an emphasis on the critical functions that MMPs have in the pathophysiology of obesity and the related diseases.

Circulating MicroRNA-505 May Serve as a Prognostic Biomarker for Hypertension-Associated Endothelial Dysfunction and Inflammation.

Our previous study has reported that the plasma microRNA-505 (miR-505) is elevated in hypertensive patients. However, the pathophysiological significance of miR-505 in hypertension remains to be elucidated. Hypertension is not only a vascular disorder, but also an inflammatory condition. The current study therefore aims to further investigate the pathophysiological implications of miR-505 in hypertension-associated vascular and inflammatory changes. In vivo experiments reveal that the plasma level of miR-505 is elevated in spontaneously hypertensive rats and angiotensin II-infused mice. In addition, miR-505 agomir treatment results in elevated blood pressure, endothelial dysfunction, increased vascular expression of inflammatory genes and renal inflammatory injuries as well as pre-activation of PBMCs in mice. In vitro experiments further demonstrate that miR-505 agomir increases the expression of IL1B and TNFA, whereas miR-505 antagomir attenuates TNF-α-induced upregulation of IL1B and TNFA in endothelial cells, HUVECs. In addition, miR-505 modulates the levels of endothelial activation markers VCAM1 and E-selectin in HUVECs as well as the adhesion of THP-1 monocytes to HUVECs. Lastly, the plasma level of miR-505 is positively correlated with systolic blood pressure and the level of C-reactive protein in human subjects. Our work links for the first time miR-505 to endothelial dysfunction and inflammation under hypertensive conditions, supporting the translational value of miR-505 in prognosticating hypertension-associated endothelial impairment and inflammatory injuries in target organs such as the vessels and kidneys.

The effects of raloxifene on endothelial function and Inflammation in Postmenopausal women: A Meta-analysis of randomized controlled trials.

Raloxifene treatment has been reported to be associated with cardiovascular benefits if prescribed to women during the postmenopausal period. However, a final conclusion regarding this hypothesis has not yet been achieved. We conducted a systematic review and meta-analysis to evaluate the effect of raloxifene on the endothelial function and inflammation in postmenopausal women. We systematically searched the following 4 databases from inception to 23 January 2021 without any language restrictions: Web of Science, PubMed/Medline, Embase and Scopus. The eligible randomized controlled trials (RCTs) reporting the effects of raloxifene on the flow-mediated dilatation (FMD), C-reactive protein (CRP), carotid intima-media thickness (CIMT), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and E-selectin levels, were included in the final meta-analysis. A total of 16 RCTs were included in the final analysis. Raloxifene administration had no significant effect on ICAM-1 and E-selectin levels. However, we observed a decrease of the CIMT (WMD: -0.071mm, 95% CI: -0.09 to -0.04, P=0.000), CRP (WMD: -0.342mg/L, 95% CI: -0.591, -0.094, p=0.007), and VCAM-1 (WMD: -197.90mg/L, 95% CI: -269.58 to -126.23, P=0.000) levels in the intervention versus control groups following the prescription of this pharmacological agent. Moreover, raloxifene treatment resulted in a significant elevation of the FMD (WMD: 1.64%, 95% CI: 0.46 to 2.81, P=0.006), particularly if the intervention was equal to or exceeded 12weeks. Raloxifene might emerge as a potential therapeutic option in the management of endothelial dysfunction and inflammation in postmenopausal women.

Abstract P092: Cell Adhesion Molecules And Incident Hypertension In Black And White Adults: The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Background: High C-reactive protein (a nonspecific inflammatory biomarker) is a risk factor for incident hypertension. The role of specific inflammation pathways in hypertension’s origins are unresolved. E-selectin, ICAM-1, and VCAM are cell adhesion molecules expressed by endothelial cells that aid leukocyte adhesion during inflammation. Their association with incident hypertension is unclear. Objective: To determine risk of incident hypertension by level of E-selectin, ICAM-1, and VCAM. Methods: REGARDS enrolled 30,239 Black and White US adults aged ≥45 years from across the continental US in 2003-2006, with a second exam in 2013-2016. The Biomarkers as Mediators of Racial Disparities in Risk Factors (BioMedioR) study included 4,400 REGARDS participants who attended both exams. We excluded participants with hypertension or missing biomarkers of interest at baseline. Hypertension was defined using a 140/90 mm Hg threshold or self-reported use of blood pressure (BP) lowering medications. Modified Poisson regression estimated relative risk (RR) of incident hypertension by baseline E-Selectin, ICAM-1, and VCAM. Results: Among 1,923 normotensive participants (mean [SD] age 71 [8] years, 36% Black race, 51% women) with 9 years median follow up, 37% developed hypertension. Baseline E-selectin and ICAM-1 but not VCAM were higher among Black participants and obese participants. In multivariable adjusted models, higher E-selectin was associated with greater risk of incident hypertension among White but not Black adults (P interaction = 0.05) in all but the final model ( Table ). Higher ICAM-1 and VCAM were not associated with risk of hypertension in any model. Conclusion: In a prospective study of Black and White US adults, E-selectin was associated with incident hypertension among White adults except when adjusting for medical comorbidities, including baseline systolic BP. Modification of E-selectin through behavioral interventions or medical therapies might be tested to lower risk of hypertension development.

Influence of hydroxychloroquine blood levels on adhesion molecules associated with endothelial dysfunction in patients with systemic lupus erythematosus

BackgroundPatients with SLE have an endothelial dysfunction (ED), which is considered the earliest marker of cardiovascular (CV) disease. Endothelial cell activation induced by proinflammatory cytokines is defined by the endothelial...

Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity

Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 h of presentation with a TIA or AIS. CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Patients with TIA and AIS have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.

Acute-Phase Inflammatory Reaction Predicts CMR Myocardial Scar Pattern and 2-Year Mortality in STEMI Patients Undergoing Primary PCI.

(1) Background: The inflammatory response following MI plays an important role in the healing, scar formation, and left ventricle (LV) remodeling. Cardiac magnetic resonance (CMR) imaging can accurately quantify the extent of myocardial scarring. The study aimed to investigate: (a) the relationship between acute inflammatory response and the CMR parameters of the scarring extent, and (b) the predictive power of inflammatory biomarkers and myocardial scarring for 2-year mortality. (2) Methods: The study included 202 STEMI patients, who underwent pPCI. Serum hs-CRP, IL-6, P-selectin, E-selectin, I-CAM, and V-CAM levels were determined at admission, and hs-CRP on the fifth day. Patients underwent LGE-CMR after 1 month, for LV volumes, ejection fraction (EF), infarct size (IS), and transmurality. Subjects were divided into tertiles according to the IS, and 2-year all-cause mortality was determined. (3) Results: IL-6 was associated with IS (r = 0.324, p = 0.01), increased transmurality index (r = 0.3, p = 0.01), and lower LVEF (r = −0.3, p = 0.02). Admission hs-CRP levels were not associated with IS, transmurality, or mortality, while hs-CRP at day 5 was a significant predictor for IS (AUC = 0.635, p = 0.05) as well as IL-6 levels (AUC = 0.685, p < 0.001). Mortality was significantly higher in the upper IS tertiles (6% vs. 8.7% vs. 24.52%, p = 0.005). IS was a significant predictor of 2-year mortality (AUC = 0.673, p = 0.002), with a cut-off value of 28.81 g, as well as high transmurality (AUC = 0.641, p = 0.013), with a cut off value of 18.38 g. (4) Conclusions: The serum levels of IL-6 and day-5 hs-CRP predict IS and transmurality, and day-5 hs-CRP levels are independent predictors of 2-year mortality in STEMI patients treated with pPCI. The CMR pattern of myocardial scarring after 1 month, as expressed by the magnitude of IS and transmurality, is a significant predictor for 2-year mortality after revascularized STEMI.

Carabin Deficiency Aggravates Hepatic Ischemia-Reperfusion Injury Through Promoting Neutrophil Trafficking via Ras and Calcineurin Signaling.

Neutrophil infiltration plays an important role in the initial phase of hepatic ischemia and reperfusion injury (HIRI). Despite many different key molecules that have been reported to meditate neutrophil trafficking in HIRI, the mechanism of this process has not been fully elucidated. In this study, we found that Carabin deficiency in myeloid cells (LysMCre : Carabinfl/fl) aggravated IRI-induced hepatic injury and apoptosis through increasing the infiltration of CD11b+Ly6G+ neutrophils. ImmGen Datasets further revealed that Carabin was expressed in bone marrow neutrophils (GM.BM) but was significantly downregulated in thio-induced peripheral neutrophils (GN.Thio.PC), which was consistently verified by comparing GM.BM and liver-infiltrating neutrophils induced by IRI. Mechanistically, up-regulation of Carabin in GM.BM in vitro reduced the expression levels of P-selectin, E-selectin, and αvβ3 integrin through inhibiting Ras-ERK and Calcineurin-NFAT signaling. Furthermore, blocking P-selectin, E-selectin, and αvβ3 integrin in LysMCre : Carabinfl/fl mice decreased the frequency and number of CD11b+Ly6G+ neutrophils and reversed hepatic ischemia−reperfusion damage. In conclusion, our results provide a new understanding of Carabin, such that it is expressed and functions not only in adaptive immune cells (T and B cells) but also in innate immune cells (neutrophils), contributing to the migration of neutrophils. These findings provide novel and promising therapeutic targets for the prevention of HIRI during liver transplantation or hepatic surgery.

Possible pathway for heart failure with preserved ejection fraction prevention and treatment: the angiotensin-converting enzyme inhibitor effect on endothelial function in comorbid patients.

Aim To evaluate the effect of perindopril on the endothelial function and levels of endothelial dysfunction markers in groups of patients with heart failure with preserved (HFpEF) and mid-range (intermediate) left ventricular ejection fraction (HFmrEF).Material and methods 40 patients with HFpEF (n=20) and HFmrEF (n=20) were evaluated. At baseline, parameters of the morpho-functional state of large blood vessels and of microvessels were evaluated with photoplethysmography, and levels of E-selectin and endothelin-1 (ET-1) were measured. The patients were prescribed perindopril, and after 12 months of treatment, photoplethysmographic parameters and endothelial dysfunction markers were determined again.Results After 12 months of the perindopril treatment, improvements in the endothelial function of both large blood vessels and microvessels were noted. The phase shift increased from 10.1 to 10.9 ms in the HFpEF group (р=0.001) and from 8.35 to 9.65 ms in the HFmrEF group (р=0.002). Furthermore, the occlusion index increased from 1.45 to 1.75 in patients with HFpEF (р=0.004) and from 1.5 to 1.75 in patients with HFmrEF (р=0.010). The Е-selectin concentration decreased in both groups, from 57.25 to 42.4 ng/ml (р=0.00008) and from 40.5 to 35.7 ng/ml (р=0.010) in patients with HFpEF and HFmrEF, respectively. The ET-1 concentration decreased from pg/ml (р=0.010) in patients with HFpEF whereas in patients with HFmrEF, there was no significant change in the ET-1 concentration after 12 months of the perindopril treatment.Conclusion At 12 months, the endothelial function improved and E-selectin and ET-1 levels decreased in patients with HFpEF and HFmrEF.

Leptin and PCSK9 concentrations are associated with vascular endothelial cytokines in patients with stable coronary heart disease.

Leptin and proprotein convertase subtilisin kexin 9 (PCSK9) play an important role in regulating blood lipid concentration. Recently, they have been found to show the ability to independently regulate the immune response. Vascular immune response has an important pathological function in the development of coronary heart disease (CHD) and thrombosis. The aim of this study was to explore the relationship between leptin, PCSK9, and vascular endothelial cell related inflammatory factors. First, detailed clinical information were collected and analyzed for 27 patients with stable CHD and corresponding 27 healthy controls. Second, using liquid-phase protein chip technology, leptin, PCSK9, and vascular-related inflammatory factors, such as E-selectin, vascular cell adhesion protein 1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-γ), and interleukin-17 (IL-17), were detected on the same platform. Finally, the correlation between leptin, PCSK9, and the inflammatory factors was analyzed. Through collecting clinical information of patients, it was suggested that there was a significant positive correlation between leptin and blood lipid level in CHD. Compared with healthy people, the levels of leptin, PCSK9, E-selectin, and ICAM-1 were significantly high in patients with CHD. There was a high positive correlation between leptin and E-selectin, ICAM-1, IFN-γ, and IL-17. Also, a high positive correlation between PCSK9 and E-selectin, IFN-γ, and IL-17 concentrations was observed. In general, leptin and PCSK9 may not only be able to regulate lipid metabolism, but may also be able to regulate inflammation in CHD.