Form Of Intercellular Adhesion Molecule-1 Research Articles

Effect of magnesium sulfate treatment on mediators of endothelial dysfunction and electrolytes in mild and severe preeclampsia: A case-control study.

Magnesium sulfate (MgSO4) treatment is widely used for the prevention of eclamptic seizures. However, its effect on mediators of endothelial dysfunction (ED) and electrolytes remains unclear. We evaluated the effects of MgSO4 treatment on mediators of ED and electrolytes. We recruited 100 women comprising 50 severe, 50 mild preeclampsia (PE) as cases and 50 normotensive pregnant women as controls from the Sampa Government Hospital, Ghana. We estimated for adrenomedullin (AM),calcitonin gene-related peptide (CGRP),soluble forms of intercellular adhesion molecule-1 (sICAM-1), Na+, K+, and Mg2+ before MgSO4 treatment, 24 h after MgSO4 treatment, and 48 h after delivery. p < 0.05 were considered significant for statistical analyses. Levels of AM, sICAM-1, and Na+ decreased significantly at 24 h after MgSO4 treatment and 48 h after delivery among PEwomen compared to the AM levels before treatment (p < 0.0001). The levels of CGRP and Mg2+ increased significantly after 24 h of MgSO4 treatment and 48 h after delivery among PE compared to the AM levels before treatment (p < 0.0001). The changes in AM, sICAM-1, CGRP, and Mg2+ at 24 h after treatment and 48 h after delivery were significantly higher in severe compared to mild PE (p < 0.0001). AM levels reduced significantly by 14.7% in mild and 42.7% in severe PE after MgSO₄ treatment (p < 0.05). sICAM-1 levels reduced significantly by 20.9% in mild and 25% in severe PE after MgSO₄ treatment. After MgSO₄ treatment, there was significant increase of 42.1% and >100% in CGRP levels in mild and severe PE, respectively (p < 0.05). After MgSO₄ treatment, Mg²⁺ levels increased significantly by 67.0% and 63.8% in mild and severe PE, respectively (p < 0.05). MgSO₄ treatment reduces AM, sICAM-1, and sodium levels but improves magnesium and CGRP in severe than mild PE thus have more beneficial role in severe PE.

In Vivo Magnetic Resonance Imaging-Based Detection of Heterogeneous Endothelial Response in Thoracic and Abdominal Aorta to Short-Term High-Fat Diet Ascribed to Differences in Perivascular Adipose Tissue in Mice.

BackgroundLong‐term feeding with a high‐fat diet (HFD) induces endothelial dysfunction in mice, but early HFD‐induced effects on endothelium have not been well characterized.Methods and ResultsUsing an magnetic resonance imaging‐based methodology that allows characterization of endothelial function in vivo, we demonstrated that short‐term (2 weeks) feeding with a HFD to C57BL/6 mice or to E3L.CETP mice resulted in the impairment of acetylcholine‐induced response in the abdominal aorta (AA), whereas, in the thoracic aorta (TA), the acetylcholine‐induced response was largely preserved. Similarly, HFD resulted in arterial stiffness in the AA, but not in the TA. The difference in HFD‐induced response was ascribed to distinct characteristics of perivascular adipose tissue in the TA and AA, related to brown‐ and white‐like adipose tissue, respectively, as assessed by histology, immunohistochemistry, and Raman spectroscopy. In contrast, short‐term HFD‐induced endothelial dysfunction could not be linked to systemic insulin resistance, changes in plasma concentration of nitrite, or concentration of biomarkers of glycocalyx disruption (syndecan‐1 and endocan), endothelial inflammation (soluble form of vascular cell adhesion molecule 1, soluble form of intercellular adhesion molecule 1 and soluble form of E‐selectin), endothelial permeability (soluble form of fms‐like tyrosine kinase 1 and angiopoietin 2), and hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1).ConclusionsShort‐term feeding with a HFD induces endothelial dysfunction in the AA but not in the TA, which could be ascribed to a differential response of perivascular adipose tissue to a HFD in the AA versus TA. Importantly, early endothelial dysfunction in the AA is not linked to elevation of classical systemic biomarkers of endothelial dysfunction.

Development, validation and application of a micro–liquid chromatography–tandem mass spectrometry based method for simultaneous quantification of selected protein biomarkers of endothelial dysfunction in murine plasma

The objective of this study was to develop and validate the method based on micro–liquid chromatography–tandem mass spectrometry (microLC/MS–MRM) for simultaneous determination of adiponectin (ADN), von Willebrand factor (vWF), soluble form of vascular cell adhesion molecule 1 (sVCAM–1), soluble form of intercellular adhesion molecule 1 (sICAM–1) and syndecan–1 (SDC–1) in mouse plasma. The calibration range was established from 2.5pmol/mL to 5000pmol/mL for ADN; 5pmol/mL to 5000pmol/mL for vWF; 0.375pmol/mL to 250pmol/mL for sVCAM–1 and sICAM–1; and 0.25pmol/mL to 250pmol/mL for SDC–1. The method was applied to measure the plasma concentration of selected proteins in mice fed high–fat diet (HFD), and revealed the pro–thrombotic status by increased concentration of vWF (1.31±0.17 nmol/mL (Control) vs 1.98±0.09 nmol/mL (HFD), p <0.05) and the dysregulation of adipose tissue metabolism by decreased concentration of ADN (0.62±0.08 nmol/mL (Control) vs 0.37±0.06 nmol/mL (HFD), p <0.05). In conclusion, the microLC/MS–MRM–based method allows for reliable measurements of selected protein biomarkers of endothelial dysfunction in mouse plasma.

Increased Levels of sENG and sVCAM-1 and Decreased Levels of VEGF in Severe Preeclampsia.

Preeclampsia (PE) is characterized by hypertension and proteinuria after the 20th week in pregnant women who have had no previous symptoms. Clinically, it is important to diagnose the severe form of the disease, in which blood pressure is much higher. Imbalance between angiogenic and antiangiogenic factors, as well as changes in adhesion molecules seem to contribute to the endothelial dysfunction and PE clinical manifestations. The aim of this study was to assess plasma levels of the angiogenic factors (free vascular endothelial growth factor (VEGF) and soluble endoglin (sEng)) and adhesion molecules (soluble forms of intercellular adhesion molecule-1 (sICAM-1) and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1)) in severe PE (sPE), in order to clarify the circulating profile of these factors. Sixty women with sPE (34 with early sPE and 26 with late sPE), and 60 normotensive pregnant were enrolled in this study. Free VEGF, sICAM-1, sVCAM-1, and sEng plasma levels were determined by ELISA. Increased sEng and sVCAM-1 and decreased free VEGF plasma levels were found in women with sPE, compared with normotensive pregnant group. However, no significant difference was observed comparing early and late sPE. Our data confirm the imbalance in changes in angiogenic and antiangiogenic factors, as well changes in adhesion molecule (sVCAM-1) in PE. These findings give support to the hypothesis that circulating angiogenic proteins and endothelial dysfunction may have an important biologic role in PE. Data from prospective, longitudinal studies producing serial determinations of these molecules throughout pregnancy are needed to better understanding the relevance of these markers in PE diagnosis and prognosis.

DYNAMICS OF PARAMETERS OF PROINFLAMMATORY ACTIVATION IN PATIENTS WITH HYPERTENSION UNDER INFLUENCE OF CANDESARTAN THERAPY

Aim. Proinflammatory activation is one of the possible pathogenetic mechanisms of formation and progression of hypertension. 107 patients with essential hypertension (EH) II stage was included into the study of the pro-inflammatory activation. Methods and results. Levels of C-reactive protein (CP), α-tumor necrosis factor (α-TNF) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in the serum were studied by ELISA before and after 12 weeks of treatment with candesartan. 31 healthy subjects were included in the control group. It is found that C-reactive protein in 5,18 times (p<0,05), α-tumor necrosis factor on the 39,04% (p<0,05) and sICAM-1 to 41, 87% (p<0,05) higher in hypertensive patients with stage II than those of the control group. Significant reductions of CRP in the blood serum by 70,33%, α-TNF – by 19,94% and sICAM-1 inserum by 18,46% compared to baseline (p<0,05) were found under the influence of candesartan therapy. Conclusion. These data indicate the presence of activation of proinflammatory processes in hypertensive patients with significant progression according to the degree of blood pressure and additional anti-inflammatory properties of candesartan.

Increased levels of exhaled sICAM1, sVCAM1, and sE-selectin in patients with non-small cell lung cancer

The mortality of lung cancer remains high and methods for early diagnosis are still lacking. Recently, exhaled breath condensate (EBC) has been considered a potential tool for obtaining biological information leading to a reliable diagnosis of non-small cell lung cancer (NSCLC). This study assessed the potentials of exhaled and serum concentrations of soluble(s) forms of intercellular adhesion molecule 1 (sICAM1), vascular cell adhesion molecule 1 (sVCAM1), and E-selectin as biomarkers for diagnosis and predicting metastasis in NSCLC patients. We enrolled 33 patients with NSCLC, 35 patients with chronic obstructive pulmonary disease (COPD) and 30 healthy controls. EBC and serum samples from subjects were collected at the time of diagnosis and, where applicable, 3 months after surgical treatment. Measurements of sICAM1, sVCAM1, and sE-selectin were determined by enzyme immunoassay. Concentrations of sICAM1, sVCAM1, and sE-selectin in the EBC and sera of NSCLC patients were significantly elevated compared to COPD patients and healthy controls. The exhaled and serum levels of sICAM1 and sVCAM1, but not sE-selectin, decreased significantly after tumor resection from pre-surgery levels. In addition, analyzed results showed a correlation between exhaled sICAM1 levels and disease progression of NSCLC patients. Our results suggest that the levels of sICAM1, sVCAM1, and sE-selectin in EBC and sera of NSCLC patients are higher than those of COPD patients or healthy controls. Moreover, exhaled sICAM1 may have prognostic value and potential as a biomarker for the diagnosis and prognosis of patients with lung cancer.

A Potential Role for Plasma Uric Acid in the Endothelial Pathology of Plasmodium falciparum malaria

BackgroundInflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, ‘parasite-derived’ uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria.Methodology/Principal FindingsWe measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5–17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels.Conclusions/SignificanceElevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in which activated thrombin induces fibrin deposition and platelet aggregation in microvessels. This protocol is registered at clinicaltrials.gov (NCT00669084).

Endothelium injury and inflammatory state during abdominal aortic aneurysm surgery: scrutinizing the very early and minute injurious effects using endothelial markers – a pilot study

IntroductionOne of the most severe complications of repair surgery for abdominal aortic aneurysms (AAA) is acute kidney injury (AKI). Acute kidney injury is an inflammatory process whose pathogenesis involves endothelial cells (EC). The aim of this study was to assess the dynamics of endothelium injury markers measured during elective AAA surgery which might confirm the inflammatory character of AKI.Material and methodsThe study group consisted of 14 patients with AAA. We measured plasma soluble forms of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin as well as the levels of von Willebrand factor (vWF) before, during (including intra-abdominal vein levels before and after aortic clamp removal) and within 2 days after surgery.ResultsWe have found a biphasic response of ICAM-1, VCAM-1 and P-selectin with an initial fall and subsequent rise. However, only VCAM-1 changes were significant compared to its baseline value. The maximum decrease of VCAM-1 was observed in the renal vein 5 min after aortic clamp removal (335.42 ±129.63 ng/ml vs. 488.90 ±169.80 ng/ml baseline value, p < 0.05), and the highest rise 48 h after aortic clamp removal (721.46 ±333.99 vs. baseline, p < 0.05).ConclusionsVascular cell adhesion molecule-1 turned out to be the most sensitive indicator of EC injury and inflammatory status after AAA surgery. During AAA surgery, soluble forms of P-selectin, ICAM-1 and VCAM-1 demonstrate a biphasic response with an initial fall and subsequent rise. These soluble forms could have a modulatory effect on the development of inflammation.

The dominant roles of ICAM-1-encoding gene in DNA vaccination against Japanese encephalitis virus are the activation of dendritic cells and enhancement of cellular immunity

We investigated the cellular immune responses elicited by a plasmid DNA vaccine encoding prM–E protein from the Japanese encephalitis (JE) virus (JEV) with or without various forms of intercellular adhesion molecule (ICAM)-1 gene to maximize the immune responses evoked by the JE DNA vaccine. We observed that co-immunization with the construct containing murine ICAM-1 gene (pICAM-1) resulted in a significant increase in the percentage of CD4+T cells, high level of JEV-specific cytotoxic T lymphocyte response, and high production of T helper 1 (Th1)-type cytokines in splenic T cells. Furthermore, the co-expression of ICAM-1 and DNA immunogens was found to be more effective in generating T cell-mediated immune responses than those induced by immunization with pJME in combination with pICAM-1. Our results suggested that ICAM-1 enhanced T cell receptor signaling and activated Th1 immune responses in the JEV model system by increasing the induction of CD4+Th1 cell subset and activating dendritic cells.

Increase in IL-6, TNF-α, and MMP-9, but not sICAM-1, concentrations depends on exercise duration

It has been suggested that exercise intensity is of importance in the regulation of increase in pro-inflammatory molecules, but there is still a debate about the effect of duration on these molecules. Therefore, the effect of exercise duration on the serum concentrations of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), soluble form of intercellular adhesion molecule-1 (sICAM-1), and matrix metalloproteinase-9 (MMP-9) was studied in 22 half-marathon (HM) and 18 marathon (M) male amateur runners who completed their exercise task in 1.8 ± 0.2 (mean ± standard deviation) and 3.6 ± 0.4 h, respectively (thus, average speed was 11.7 ± 1.5 and 11.9 ± 1.8 km h(-1), respectively). Blood was sampled 2 days before, 15 min after, and 28 h after the race. IL-6, TNF-α, and MMP-9 always increased immediately after exercise, but the increase was larger (P < 0.05) in M versus HM (∆IL-6: 31 ± 24 vs. 5 ± 4 pg ml(-1); ∆TNF-α: 1.7 ± 1.9 vs. 0.5 ± 0.8 pg ml(-1); MMP-9: 288 ± 216 vs. 145 ± 128 ng ml(-1), respectively). sICAM-1 also increased with exercise, but similarly in M and HM (20 ± 40 vs. 23 ± 32 ng ml(-1), respectively). Only sICAM-1 remained elevated 28 h post-exercise in both HM and M, while IL-6, TNF-α, and MMP-9 returned to pre-exercise levels. Competitive HM and M races induce significant increases in IL-6, TNF-α, sICAM-1, and MMP-9 concentrations. As HM and M runners performed the competition with similar absolute intensity, the difference in response between the groups suggests that exercise duration is of importance in the regulation of IL-6, TNF-α, and MMP-9, but not sICAM-1 concentrations in response to prolonged running.

Social relationships and inflammatory markers: An analysis of Taiwan and the U.S.

We evaluated the association between two aspects of social relationships and six inflammatory markers in Taiwan and the U.S. These two countries share similar levels of current life expectancy, but exhibit important differences in social structure. The data comprised population based samples from Taiwan (aged 53+; n=962) and the U.S. (aged 35–86; n=990) collected between 2003 and 2009. Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), fibrinogen, and soluble forms of intercellular adhesion molecule 1, E-selectin, and IL-6 receptor (sIL-6R) were measured in fasting blood samples. A social integration score was based on marital status, contact with family and friends, church attendance, and other social participation. A perceived social support index was based on questions regarding the availability of care and support from family and friends. Linear regression models tested the association between these two measures and each inflammatory marker controlling for sociodemographic characteristics, obesity, medication use, and baseline health status. After adjusting for potential confounders, social integration had a significant but weak inverse association with CRP in Taiwan. Perceived social support was significant in two of 12 models, and the coefficient was positive (i.e., higher support was associated with higher CRP and sIL-6R in the U.S.). We found no evidence that the coefficients for social relationship measures varied by sex or age. Our results yielded limited evidence of a weak association between two dimensions of social relationships and six inflammatory markers in Taiwan and the U.S. Given that the literature suggests a strong link between social relationships and mortality, and that inflammation plays an important role in the leading causes of death, we had expected to find consistent and moderately strong associations between social relationships and inflammatory markers. The small effect sizes and lack of robustness across markers were surprising.

The effect of poloxamer 407 on the functional properties of HDL in mice

There is an inverse relationship between high-density lipoprotein (HDL) and heart disease. HDL possesses not only both antioxidant and anti-inflammatory properties, but also anti-thrombotic and endothelial function-promoting qualities. However, it is not only the serum concentration of HDL that is important, but also the 'functional' quality of the HDL. The objective was to determine the functional status of HDL in a well-established mouse model of dyslipidaemia and atherosclerosis induced by the administration of a block copolymer (poloxamer 407; P-407). C57BL/6 mice were administered a single intraperitoneal dose of P-407 (0.5g/kg) and blood was collected at 24h post-dosing. HDL was isolated from controls (control HDL) and P-407-treated (P-407 HDL) mice and used to test its anti-inflammatory properties in vitro. Additionally, antioxidant enzymes associated with HDL, namely, platelet activating factor-acetylhydrolase (PAF-AH) and paraoxonase (PON), were evaluated for any potential reduction in their biological activity. A single injection of P-407 in C57BL/6 mice resulted in a marked decrease in the levels of HDL-cholesterol and phospholipids. HDL particle size significantly increased, primarily due to remodelling of HDL with triglyceride. It was demonstrated that (i) long-chain saturated fatty acids were higher and the n-3/n-6 fatty acid ratio was significantly lower for P-407 HDL compared with control HDL, and (ii) P-407 HDL lost its capacity to inhibit tumour necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expression compared with control HDL. Additionally, P-407 HDL was not able to neutralize lipopolysaccharide and inhibit subsequent TNF-α production compared with control HDL. The biological activity of platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase (PON) decreased in direct proportion to the circulating levels of both HDL-cholesterol and apolipoprotein (apoA-1). Combination of previously reported findings in P-407-treated mice, such as (i) production of both oxidized LDL and malondialdehyde, and (ii) profound elevations in the soluble forms of intercellular adhesion molecule-1 (ICAM-1), VCAM-1, and E-selectin, with the present results, would strongly suggest that HDL in P-407-treated mice is rendered dysfunctional. Thus, these findings help to explain why P-407-treated mice begin to form aortic atherosclerotic lesions about one month after initiating P-407 treatment.

Effect of palmitic acid and linoleic acid on expression of ICAM-1 and VCAM-1 in human bone marrow endothelial cells (HBMECs).

IntroductionThe amount and type of fatty acids (FAs) in the diet influence the risk of atherosclerosis. Palmitic acid and linoleic acid exist at high levels in Iranian edible oils. In this study, we investigated the effect of palmitic acid and linoleic acid on expression of soluble and cell-associated forms of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in human bone marrow endothelial cells (HBMECs).Material and methodsThe endothelial cells were induced with bacterial lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α), and thereafter incubated with palmitic or linoleic acid. The level of soluble and cell-associated VCAM-1 and ICAM-1 were analyzed using ELISA and western blot.ResultsOur findings indicated that palmitic acid up-regulates the expression of ICAM-1 and VCAM-1 in HBMECs when these cells are induced with TNF-α or LPS. In addition, the results suggest that linoleic acid could sustain up-regulated ICAM-1 and VCAM-1 in activated endothelial cells.ConclusionsChronic activation of endothelial cells in the presence of palmitic and linoleic may account for pathogenesis of cardiovascular events. These findings provide further support for the detrimental effects of these fatty acids, especially palmitic acid, in promotion and induction of cardiovascular diseases which are prevalent in the Iranian population.

Increased leptin/leptin receptor pathway affects systemic and airway inflammation in COPD former smokers

BackgroundLeptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.MethodsWe measured the levels of leptin, tumor necrosis factor alpha (TNF-α) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.ResultsIn plasma of COPD patients, leptin was inversely correlated with TNF-α and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-α. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-α were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.ConclusionOur findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.

Dynamics of Inflammatory Markers in Post-Acute Stroke Patients Undergoing Rehabilitation

Stroke is a pathological condition associated with an enhanced inflammatory response that has a multifactorial etiology. We evaluated the dynamic of plasma concentrations of IL-1α, IL-6, IL-8, TNF-α, soluble form of intercellular adhesion molecule 1, and lipoprotein (a) [Lp(a)] during the rehabilitation of post-acute stroke patients (n = 20), in parallel with control subjects (n = 24). Stroke patients had significantly increased concentrations of IL-6, TNF-α, and Lp(a) when compared to healthy controls. It was found that the changes in the IL-6, IL-8, and TNF-α concentrations associated with the pathological condition were statistically significant (χ2 = 4.81, p = 0.028, χ2 = 10.40, p = 0.005 and χ2 = 6.73, p = 0.034, respectively). The decrease of Lp(a) during the rehabilitation had statistical significance (p = 0.043), while the decrease of IL-1α had marginal significance (p = 0.071). IL-1α, TNF-α, and Lp(a) concentrations were significantly negatively correlated with the Barthel index values, suggesting that the decrease of these inflammatory markers was beneficial for patients' recovery.

Distribution and Cardiovascular Risk Correlates of Plasma Soluble Intercellular Adhesion Molecule-1 Levels in Asymptomatic Young Adults from a Biracial Community: The Bogalusa Heart Study

That circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) is associated with an increased risk for coronary artery disease is well recognized. However, information is scant regarding the distribution and cardiovascular (CV) risk correlates of sICAM-1 in asymptomatic young adults. Plasma sICAM-1 was measured in 1,184 black and white persons in the Bogalusa Heart Study cohort (70% white, 43% male), aged 24 to 44 years. CV risk was assessed in terms of CV risk factors, status of parental CV disease, and composite carotid intima-media thickness (IMT). sICAM-1 levels displayed race difference (whites > blacks, p<0.0001), but no sex difference. In multivariate analysis including age, race, sex, smoking status, waist circumference, mean arterial pressure, low- and high-density lipoprotein (LDL and HDL) cholesterols, triglycerides, insulin resistance index, C-reactive protein (CRP), and adiponectin, the significant predictors of sICAM-1, in order of entry, were race (white > black), smoking, CRP, and waist circumference. Furthermore, there was a smoking by waist circumference interaction in that smoking attenuated the magnitude of correlation between waist circumference and sICAM-1. Levels of sICAM-1 adjusted for age, race, sex, and smoking increased with number of metabolic syndrome components (p for trend<0.01); positive family history of CV disease (p<0.05); and increased in composite carotid IMT specific for age, race, and sex (p for trend<0.05). These findings underscore the potential value of plasma sICAM-1 as an additional biomarker for CV risk among asymptomatic young adults.

Intercellular adhesion molecule-1 (ICAM-1) expression and soluble ICAM-1 (sICAM-1) production by cytokine-activated human aortic endothelial cells: a possible role for ICAM-1 and sICAM-1 in atherosclerotic aortic aneurysms.

The interactions of inflammatory cells, cytokines, and cell adhesion molecules (CAM) may be important in the pathogenesis of vascular diseases such as abdominal aortic aneurysms (AAA), in which inflammation plays a role. The aim of this study was to investigate the pathogenic role of ICAM-1, a molecule involved in leucocyte-endothelial interactions, in vascular inflammation. ELISA of human explant culture supernatants revealed a four-fold increase in sICAM-1 production by AAA (n = 9) versus normal (n = 8) aortic explants. Human aortic endothelial cell (hAEC) culture was used for further studies as an in vitro model for aortic inflammatory conditions. Tumour necrosis factor-alpha (TNF-alpha) or IL-1 beta treatment of hAEC resulted in an up to 1.8-fold significant increase in sICAM-1 production compared with resting cells. In addition, the expression of ICAM-1 on cytokine-stimulated versus resting hAEC was measured by radioimmunoassay. TNF-alpha significantly induced ICAM-1 expression on these cells. These results suggest that different forms of ICAM-1, present on or released by the activated aortic endothelium, may be involved in leucocyte adhesion to and migration into the vessel wall.

A link between sICAM-1, ACE and parietal blood flow in the aging brain

A connection between Alzheimer's disease (AD) and endothelium pathology has been inferred from measured decreases in both blood flow and metabolism in the parietal and temporal cortex. However, it is not known whether these alterations are seen in normal aging. We performed regional cerebral blood flow (rCBF) measurements in 22 AD patients and in 44 non-demented subjects during a simple test of information processing speed. Cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble form of intercellular adhesion molecule-1 (sICAM-1) were analyzed in non-demented subjects. We found correlations between sICAM-1 and ACE ( p = 0.004), and sICAM (but not ACE) and CSF/plasma albumin ratio ( p < 0.0001). Higher concentrations of sICAM-1 (>893 ng/L) and ACE (>5.22 μg/L) were exclusively associated with lower parietal blood flow ( p < 0.001). The rCBF patterns in the AD and non-demented subjects with biomarker levels above median showed similar reductions in the temporoparietal areas. Our findings provide evidence that elevated CSF sICAM-1 and ACE are associated with lower perfusion levels in the parietal cortex of cognitively intact elderly.

Raloxifene slows down the progression of intima-media thickness in postmenopausal women

To investigate the effect of raloxifene on atherosclerosis progression in healthy postmenopausal women. In a prospective fashion, a total of 155 healthy postmenopausal women were randomly assigned to receive raloxifene 60 mg/day or a matching placebo for 18 months. Atherosclerosis progression was evaluated by B-mode ultrasonography measuring the intima-media thickness (IMT) of the carotid arteries. Plasma levels of triglycerides, low-density lipoprotein cholesterol, soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, E-selectin, interleukin-6, tumor necrosis factor alpha, adiponectin, and the degree of insulin resistance by the homeostatic model assessment method were also determined. The progression slope of carotid IMT was 0.0112 mm/18 months in the raloxifene group and 0.0857 mm/18 months in the placebo group (P<0.004). Raloxifene treatment compared with placebo produced a significant decrease in plasma triglycerides (P<0.02), low-density lipoprotein cholesterol (P<0.02), soluble forms of intercellular adhesion molecule-1 (P<0.005) and vascular cell adhesion molecule-1 (P<0.04), E-selectin (P<0.02), interleukin-6 (P<0.005), tumor necrosis factor alpha (P<0.005) levels, and homeostatic model assessment index (P<0.005) and a significant increase in plasma adiponectin levels (P<0.001). Logistic regression analysis indicated that women receiving raloxifene had a lower risk of IMT progression (odds ratio=0.41; 95% CI: 0.32-0.70). Raloxifene treatment, possibly through an increase in plasma adiponectin levels, may slow the progression of IMT in postmenopausal women.

Substance P enhances soluble ICAM‐1 release from adult rat cardiac fibroblasts by a p42/44 MAPK‐ and PKC‐mediated mechanism

Substance P, a pro-inflammatory neuropeptide, is released from cardiac peptidergic nerves under conditions like ischemia but whether it modulates inflammatory processes in the heart remains unexplored. This study demonstrates for the first time that substance P augments the production of the soluble form of intercellular adhesion molecule-1, sICAM-1, by adult rat cardiac fibroblasts. However, RT-PCR showed no concomitant increase in ICAM-1 transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional/translational mechanisms. Use of pharmacological inhibitors revealed that the stimulatory effect of substance P on sICAM-1 production is mediated by p42/44 MAPK and protein kinase C. Preliminary experiments also showed that the neuropeptide stimulates the production of prostaglandin E(2) by cardiac fibroblasts. The findings support the postulation that substance P may modulate multiple inflammatory responses within the myocardium through release of pro-inflammatory mediators from resident fibroblasts.