Elevated Expression of Serum Endothelial Cell Adhesion Molecules in COVID-19 Patients.

In a retrospective study of 39 COVID-19 patients and 32 control participants in China, we collected clinical data and examined the expression of endothelial cell adhesion molecules by enzyme-linked immunosorbent assays. Serum levels of fractalkine, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular adhesion protein-1 (VAP-1) were elevated in patients with mild disease, dramatically elevated in severe cases, and decreased in the convalescence phase. We conclude the increased expression of endothelial cell adhesion molecules is related to COVID-19 disease severity and may contribute to coagulation dysfunction.

VCAM-1, ICAM-1 and selectins in gestational diabetes mellitus and the risk for vascular disorders.

Aim: Levels of VCAM-1, ICAM-1 and selectins in gestational diabetes mellitus (GDM) subjects are an indication of endothelial dysfunction predicting the future metabolic consequence via metabolic memory effect. Materials & methods: This cross-sectional study was conducted in 92 pregnant women and serum endothelial cell adhesion molecules were measured using Randox biochip analyzer. Results: Significantly elevated serum level of VCAM-1 was found in GDM subjects and in greater than equal to one parity categorized GDM group when compared with control. The correlation of parity and P-selectin was statistically significant in GDM subjects. Conclusion: Elevated levels of endothelial cell adhesion molecules in GDM women indicate an imbalance in vascular function. Transient hyperglycemia during pregnancy may induce persistent modifications to the memory cells and GDM subjects are more prone to develop future consequences.

Metabolic-hypoxic modulation of cytokine induction of intestinal endothelial adhesion molecules: Relevance to ischemic injury mediated necrotizing enterocolitis?

BACKGROUND: Necrotizing enterocolitis (NEC) triggers an intense inflammatory response in the neonatal gut associated with cytokine activation, altered nutrient status and intracellular O2-deprivation. Endothelial cell adhesion molecules (ECAMs) play critical roles in driving immune cell infiltration into inflamed gut. Currently, relationships between inflammation, metabolism and ECAM expression remain poorly understood in NEC. We studied the effects of metabolic depletion (aglycemia/ hypoxia) on TNF-α mediated ECAM expression including ICAM-1, MAdCAM-1, VCAM-1 and E-selectin, in vitro in intestinal microvascular endothelial cells (IMEC). METHODS: To study the effects of TNF-α, aglycemia and hypoxia (alone or in combination) IMECs expression of adhesion molecules was studied using cell surface ELISA and immunoblotting. RESULTS: Total VCAM-1 expression was induced TNF-α and by hypoxia + TNF-α, cell surface expression was induced by hypoxia, TNF-α, TNF- α+hypoxia, and TNF- α+hypoxia and aglycemia. Total ICAM-1 increased following TNF- α, TNF- α+hypoxia, hypoxia + aglycemia, and TNF- α+hypoxia + aglycemia. Total MAdCAM-1 protein expression was significantly induced by a combination of TNF-α+hypoxia + aglycemia and cell surface expression induced by TNF- α+hypoxia. Surface expression of E-selectin was induced by TNF- α+aglycemia and TNF- α+hypoxia + aglycemia. CONCLUSION: Energy metabolism influences inflammation induced injury through mobilization of intestinal ECAMs, and may represent an important mechanism in NEC pathology.

Posttraumatic stress disorder onset and inflammatory and endothelial function biomarkers in women.

BACKGROUND: Research has linked posttraumatic stress disorder (PTSD) with higher circulating levels of inflammatory and endothelial function (EF) biomarkers, and effects may be bidirectional. We conducted the first investigation of new-onset PTSD and changes in inflammatory and EF biomarkers. METHODS: Data were from women in the Nurses' Health Study II. Biomarkers obtained at two blood draws, 10-16 years apart, included C-reactive protein (CRP), tumor necrosis factor-alpha receptor-II (TNFRII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). PTSD was assessed via interview. Analyses compared biomarker levels in women with PTSD that onset between draws (n = 175) to women with no history of trauma (n = 175) and to women with history of trauma at draw 1 and no PTSD at either draw (n = 175). We examined if PTSD onset was associated with biomarker change over time and if pre-PTSD-onset biomarker levels indicated risk of subsequent PTSD using linear mixed models and linear regression, respectively. Biomarkers were log-transformed. RESULTS: Compared to women without trauma, women in the PTSD onset group had larger increases in VCAM-1 over time (b = 0.003, p = .068). They also had higher TNFRII (b = 0.05, p = .049) and ICAM-1 (b = 0.04, p = .060) levels at draw 1 (prior to trauma and PTSD onset). However, pre-PTSD-onset biomarker levels did not predict onset of more severe PTSD. CONCLUSIONS: PTSD onset (vs. no trauma) was associated with increases in one inflammation-related biomarker. Effects may be small and cumulative; longer follow-up periods with larger samples are needed. We did not observe strong support that pre-PTSD-onset biomarkers predicted risk of subsequent PTSD.

Effect of soluble factors derived from ZR 75.30 breast cancer cells on endothelial activation.

In this study, we analyzed soluble factors secreted by two Estrogen Receptor Positive (ER-α) human breast cancer cell lines, ZR 75.30 (luminal B) and MCF7 (luminal A), and evaluated their effect on endothelial activation. The composition of tumoral soluble factors (TSFs) was analyzed by ELISA (Bio-Plex). TSFs from ZR 75.30 cells expressed higher levels of TNF, IFN-γ, IL-6, and IL-8 compared to TSFs from MCF-7 cells. TSFs from ZR 75.30 cells induced a pro-adhesive phenotype in human umbilical vein endothelial cells (HUVECs), as characterized by increased monocytic cell adhesion, adhesion molecule expression and NF-κB activation and decreased IκB-α expression. Conversely, TSFs from MCF-7 cells exerted none of these effects on HUVECs. We then added TNF, IFN-γ, IL-6 or IL-8 alone or in combination with TSFs from MCF-7 cells to HUVECs. Only the combinations that included TNF induced endothelial activation. A neutralizing antibody against IL-1ß (this cytokine was not measured in the ELISA) had a modest blocking effect on cellular adhesion or the expression of adhesion molecules induced by TSFs from ZR 75.30 cells in HUVECs. However neutralizing antibodies against TNF, IFN-γ, IL-6 or IL-8 had no effect. Our results suggest that although TNF is an inducer of endothelial cell activation, it is not the only molecule that is responsible for this effect in TSFs from ZR 75.30 cells.

Cross-Sectional and Longitudinal Associations of Chronic Posttraumatic Stress Disorder With Inflammatory and Endothelial Function Markers in Women.

BACKGROUND: Posttraumatic stress disorder (PTSD) may contribute to heightened cardiovascular disease risk by promoting a proinflammatory state and impaired endothelial function. Previous research has demonstrated associations of PTSD with inflammatory and endothelial function biomarkers, but most work has been cross-sectional and does not separate the effects of trauma exposure from those of PTSD. METHODS: We investigated associations of trauma exposure and chronic PTSD with biomarkers of inflammation (C-reactive protein and tumor necrosis factor alpha receptor II) and endothelial function (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in 524 middle-aged women in the Nurses' Health Study II. Using linear mixed models, we examined associations of trauma/PTSD status with biomarkers measured twice, 10 to 16 years apart, in cardiovascular disease-free women, considering either average levels over time (cross-sectional) or change in levels over time (longitudinal). Biomarker levels were log-transformed. Trauma/PTSD status (based on structured diagnostic interviews) was defined as no trauma at either blood draw (n = 175), trauma at blood draw 1 but no PTSD at either draw (n = 175), and PTSD that persisted beyond blood draw 1 (chronic PTSD; n = 174). The reference group was women without trauma. RESULTS: In models adjusted for known potential confounders, women with chronic PTSD had higher average C-reactive protein (B = 0.27, p < .05), tumor necrosis factor alpha receptor II (B = 0.07, p < .01), and intercellular adhesion molecule-1 (B = 0.04, p < .05) levels. Women with trauma but without PTSD had higher average tumor necrosis factor alpha receptor II levels (B = 0.05, p < .05). In addition, women with chronic PTSD had a greater increase in vascular cell adhesion molecule-1 over time (B = 0.003, p < .05). CONCLUSIONS: Increased inflammation and impaired endothelial function may be pathways by which chronic PTSD increases cardiovascular disease risk.

Zinc oxide nanoparticle-induced atherosclerotic alterations in vitro and in vivo.

Engineered zinc oxide nanoparticles (ZnO-NPs) are currently being produced in high tonnage. Exposure to ZnO-NPs presents potential risks to cardiovascular system. Thus far, the toxicological effects of ZnO-NPs on cardiovascular system have not been well characterized. In this study, human coronary artery endothelial cells (HCAECs) were exposed to ZnO-NPs directly or indirectly using a transwell coculture system with human alveolar epithelial cell line A549 to mimic the lung/circulation interaction. It was shown that levels of proinflammatory mediators (interleukin-8 [IL-8] and tumor necrosis factor-α [TNF-α]) and biomarkers of atherosclerogenesis (heme oxygenase-1 [HO-1] and platelet endothelial cell adhesion molecules-1 [PECAM-1]) in the supernatants of culture media were significantly increased. Pretreatment of A549 cells on the apical side of the coculture system with the phagocytosis inhibitor cytochalasin B (CB) blocked ZnO-NP-induced HO-1 and PECAM-1 expression in HCAEC, indicating that endocytosis of ZnO-NPs by alveolar epithelial cells was involved in ZnO-NP-induced HO-1 or PECAM-1 expression in endothelial cells. Moreover, Wistar rats were intratracheally instilled with ZnO-NP suspension and high fat diet (positive control). ZnO-NP treatment induced lung and systemic inflammation, dyslipidemia, increased levels of serum HO-1 and PECAM-1, and aortic pathological damage. Taken together, exposure to ZnO-NPs could induce atherosclerotic alterations, which might involve phagocytosis of nanoparticles and inflammation in the lung.

Endothelial PECAM-1 and its function in vascular physiology and atherogenic pathology.

Platelet endothelial cell adhesion molecule (PECAM-1) is highly expressed in vascular cells such as endothelial cells (ECs) and blood-borne cells like platelets and leukocytes. In ECs, this molecule controls junctional and adhesive properties. In physiological conditions, PECAM-1 supports the endothelial barrier function. In inflammation that is observed in vessels affected by atherosclerosis, the function of PECAM-1 is impaired, an event that leads to increased adhesion of neutrophils and other leukocytes to ECs, decreased vascular integrity, and higher leukocyte transmigration to the intima media. PECAM-1 has six extracellular immunoglobulin (Ig)-like domains that support attraction and adhesion of leukocytes to ECs. The cytoplasmic tail of PECAM-1 contains two tyrosine residues (Tyr-663 and Tyr-686) that could be phosphorylated by Src family protein kinases is involved in the intracellular signaling. Actually, those tyrosines are the part of the immunoreceptor tyrosine-based inhibition motifs (ITIMs) that inhibit inflammation. However, in atherosclerosis, the PECAM-1-dependent immune suppression is disturbed. This in turn facilitates recruitment of leukocytes and supports proatherogenic inflammation.

Combination-targeting to multiple endothelial cell adhesion molecules modulates binding, endocytosis, and in vivo biodistribution of drug nanocarriers and their therapeutic cargoes.

Designing of drug nanocarriers to aid delivery of therapeutics is an expanding field that can improve medical treatments. Nanocarriers are often functionalized with elements that recognize cell-surface molecules involved in subcellular transport to improve targeting and endocytosis of therapeutics. Combination-targeting using several affinity elements further modulates this outcome. The most studied example is endothelial targeting via multiple cell adhesion molecules (CAMs), which mimics the strategy of leukocytes to adhere and traverse the vascular endothelium. Yet, the implications of this strategy on intracellular transport and in vivo biodistribution remain uncharacterized. We examined this using nanocarriers functionalized for dual- or triple-targeting to intercellular, platelet-endothelial, and/or vascular CAMs (ICAM-1, PECAM-1, VCAM-1). These molecules differ in expression level, location, pathological stimulation, and/or endocytic pathway. In endothelial cells, binding of PECAM-1/VCAM-1-targeted nanocarriers was intermediate to single-targeted counterparts and enhanced in disease-like conditions. ICAM-1/PECAM-1-targeted nanocarriers surpassed PECAM-1/VCAM-1 in control, but showed lower selectivity toward disease-like conditions. Triple-targeting resulted in binding similar to ICAM-1/PECAM-1 combination and displayed the highest selectivity in disease-like conditions. All combinations were effectively internalized by the cells, with slightly better performance when targeting receptors of different endocytic pathways. In vivo, ICAM-1/PECAM-1-targeted nanocarriers outperformed PECAM-1/VCAM-1 in control and disease-like conditions, and triple-targeted counterparts slightly enhanced this outcome in some organs. As a result, delivery of a model therapeutic cargo (acid sphingomyelinase, deficient in Niemann-Pick disease A-B) was enhanced to all affected organs by triple-targeted nanocarriers, particularly in disease-like conditions. Therefore, multi-CAM targeting may aid the optimization of some therapeutic nanocarriers, where the combination and multiplicity of the affinity moieties utilized allow modulation of targeting performance.

Asymmetric Dimethylarginine Levels are Highly Associated With Atrial Fibrillation in an Elderly Population.

BACKGROUND: The importance of endothelial dysfunction in atrial fibrillation (AF) is not clarified. The aim of this study was to evaluate endothelial dysfunction assessed by selected inflammatory and haemostatic endothelial markers and nitric oxide (NO) associated variables as related to the presence of AF in an elderly population. NO is known to express anti-thrombotic as well as vasoactive properties. METHODS: This is a cross sectional study of 75-year old subjects with AF (n = 62) and control subjects in sinus rhythm (n = 124), matched for gender. Fasting blood samples were collected for analyses of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO-synthase, L-arginine, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor (vWF). RESULTS: Levels of vWF and ADMA were significantly higher in AF patients vs controls (P = 0.023 and P < 0.001, respectively) and the L-arginine/ADMA ratios were lower (P = 0.015), the latters still significant after adjustment for relevant covariates (P = 0.007 and P = 0.037, respectively). No significant differences in the levels of VCAM-1 and E-selectin were observed between the groups. When dividing the ADMA levels into quartiles there was a significant trend for having AF with increasing levels of ADMA (P < 0.001) with a cut-off at the 25th percentile (< 0.54 µmol/L), giving an adjusted OR for having AF of 12.46 (95% CI 3.11 - 49.86) (P < 0.001) with higher levels. A similar inverse trend was seen for the L-arginine/ADMA ratio. CONCLUSION: Our population of 75-year-old AF patients had significantly impaired endothelial function assessed by increased levels of vWF, and more pronounced by high levels of ADMA. The results indicate AF in the elderly to be closely associated with the regulatory pathway of NO.

Relationship between Expression of Adhesion Molecules by Brain Microvascular Endothelial Cell and Ischemic Brain Damage (review) / 中国康复理论与实践

@#The adhesion molecules expressed by brain microvascular endothelial cell maintain the structure and function of brain, ensure the continuity of endothelium cell and penetrate blood-brain barrier in physiology. They also intervene inflammation cells that remove or orientate regular or inflammation organism in pathology. The adhesion molecules of Immunoglobulin supperfamily and Selectin family are expressed by brain microvascular endothelial cell and have affinity with the ischemic brain damage. The advance in research on relationship between the expression of adhesion molecules by brain microvascular endothelial cell and ischemic brain damage is reviewed in this article.