sVCAM-1 Concentrations Research Articles

Fetal plasma levels of circulating endothelial cell adhesion molecules in normal and preeclamptic pregnancies

Objective: Circulating levels of endothelial cell adhesion molecules are elevated in women with preeclampsia. The aim of the present study was to determine levels of these molecules in the fetal circulation of normal pregnancies and pregnancies complicated by preeclampsia. Study Design: Fetal plasma samples from the umbilical vein and peripheral maternal plasma and serum sample were collected at delivery from women with preeclampsia and women with normal pregnancy. Women with non-proteinuric pregnancy-induced hypertension (PIH) were excluded from the study. A sandwich ELISA technique was employed to quantitate concentrations of soluble ICAM-1 (CD54), VCAM-1 (CD106), and E-selectin (CD62E). Results: The normal values of soluble endothelial cell adhesion molecules in the fetal circulation were determined as 162±45 ng/ml for ICAM-1, 1612±582 ng/ml for VCAM-1, and 154±58 ng/ml for E-selectin. They were found to markedly differ from the corresponding normal values in the maternal circulation (sICAM-1: 247±65 ng/ml; sVCAM-1: 715±170 ng/ml; sE-selectin: 34±14 ng/ml). The concentrations of sICAM-1, sVCAM-1, and sE-selectin were significantly elevated in women with preeclampsia compared to healthy control pregnant women. In contrast, there was no difference in the circulating fetal concentrations of these molecules between normal pregnancies and pregnancies complicated by preeclampsia. Conclusions: Normal values of sICAM-1, sVCAM-1, and sE-selectin in fetal circulation are markedly different from the values obtained for healthy adults. Plasma concentrations of these molecules are elevated in women with preeclampsia but not in the fetal circulation of preeclamptic pregnancies suggesting that based on the analysis of soluble adhesion molecules the fetal circulation may not be affected by the factor(s) that lead to disturbed endothelial cell function in women with preeclampsia.

Increased Serum Concentrations of Soluble Vascular Cell Adhesion Molecule-1 in Uterine Cervical Cancer

The purpose of this investigation was to determine the serum concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in women with squamous cell carcinoma of the cervix. Serum samples were obtained from 38 Japanese women with squamous cell carcinoma of the cervix before initial treatment (12 in stage 0, 7 in stage I, 5 in stage II, 9 in stage III and 5 in stage IV), 7 patients with a recurrence of this cancer, and 18 healthy female volunteers. Serum sVCAM-1 was measured with a sandwich enzyme-linked immunosorbent assay. Serum concentrations (means ± SD) of sVCAM-1 in the healthy volunteers, the patients with cervical cancer in stages 0–IV and in the patients with recurrent tumors were 597.2 ± 151.4, 690.1 ± 214.2, 1,234.8 ± 466.1, 1,159.8 ± 825.8, 1,529.6 ± 662.0, 1,053.0 ± 228.8, and 1,134.8 ± 211.3 ng/ml, respectively. Values for patients with stages I–IV or recurrent cervical cancer were significantly increased compared to those for healthy volunteers (p < 0.05). Results suggest that sVCAM-1 is shed from endothelial cells in the cancerous tissue.

Levels of Circulating Adhesion Molecules in Congestive Heart Failure and After Heart Transplantation

Recent reports suggest a role for immunologic and inflammatory processes in the pathogenesis of congestive heart failure (CHF) and accelerated coronary artery disease (CAD) after heart transplantation (HT). The interaction between endothelial cells, leukocytes, and platelets involving various adhesion molecules may be of particular importance. We therefore measured serum levels of soluble(s) vascular cell adhesion molecule-1 (VCAM-1), sP-selectin, and sE-selectin in 34 patients with severe CHF (23 with CAD and 11 with idiopathic dilated cardiomyopathy) and in 20 healthy controls. Twenty of the patients were followed with serial measurements of these circulating adhesion molecules (CAMs) for up to 2 years after HT. Levels of all 3 CAMs were significantly elevated in patients with CHF compared with controls irrespective of the etiology of heart failure, with particularly high concentrations of sVCAM-1. After HT, different patterns in CAMs were found over time. Whereas there was a normalization of sE-selectin levels after HT, concentrations of sVCAM-1 also declined, but without normalization. In contrast, sP-selectin levels were persistently elevated, with the highest concentrations at the end of the study period. The persistent elevation of sP-selectin and the lack of normalization of sVCAM-1 levels were associated with persistently raised serum levels of tumor necrosis factor-α, and these findings were not related to either acute episodes of allograft rejection or intercurrent infections. These results support the notion that immunologic and inflammatory processes are important features of CHF. Furthermore, the persistently elevated levels of CAMs and tumor necrosis factor-α found up to 2 years after HT may reflect a state of persistent immune activation in these patients, possibly involved in the development of CAD after HT.

Soluble Vascular Cell Adhesion Molecule-1 in Perennial Allergic Rhinitis

Since the expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells plays a central part in the selective recruitment of eosinophils into allergic inflammatory lesions, VCAM-1 may be a key molecule in allergic inflammatory diseases. Soluble forms of VCAM-1 (sVCAM-1) have recently been identified in the circulation, but there is limited published information on levels of sVCAM-1 in the circulation. If the levels of sVCAM-1 vary between patients with allergic diseases and normal controls, this variance would be very useful to investigate the state of the allergic disease and underlying inflammation. This study investigated the serum sVCAM-1 level in patients with perennial allergic rhinitis (rhinitis group) in comparison with non-atopic healthy volunteers (control group). No significant difference in the serum sVCAM-1 level was seen between the two groups (p=0.4342). However, the serum sVCAM-1 levels in the severe rhinitis group were significantly higher than those in both the control group (p=0.0067) and the mild rhinitis group (p=0.0015), whereas no significant difference was observed between the mild rhinitis group and the control group (p=0.1113). In addition, the serum levels of sVCAM-1 were significantly correlated with the nasal symptoms in the rhinitis group (r=0.486, p<0.0001). In conclusion, serum concentrations of sVCAM-1 are increased in patients with severe perennial allergic rhinitis, and measurement of sVCAM-1 concentrations in sera is likely to be a useful tool for investigation of the severity of allergic rhinitis and underlying inflammatory reactions.

Circulating vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic NIDDM patients.

Vascular cell adhesion molecule-1 (VCAM-1) has been shown to be highly expressed in atherosclerotic lesions. Although the soluble form of VCAM-1 (sVCAM-1) is detected in human sera, the relation between the degree of atherosclerosis and serum sVCAM-1 level has not been defined. In the present study, sVCAM-1 concentrations were measured in sera from 101 Japanese NIDDM patients. The mean +/- SD serum sVCAM-1 concentration in 26 patients with symptomatic atherosclerotic vascular diseases (789 +/- 187 ng/ml) was higher than that in 75 patients without the disease (664 +/- 175 ng/ml). Among the 101 NIDDM patients, 56 had atherosclerotic change of the carotid arteries, based on the evaluation by high-resolution B-mode ultrasonography. Their sVCAM-1 level was 759 +/- 201 ng/ml, higher than that in 45 patients without any detectable atherosclerosis of the carotid arteries (619 +/- 130 ng/ml). In addition, there was a positive correlation between sVCAM-1 concentration and thickness of the intimal plus medial complex (IMT) of the carotid arteries in the NIDDM patients (r = 0.41, P < 0.0001). Multivariate regression analysis revealed significant predictors of mean IMT value to be sVCAM-1 concentration (F = 62.88, P = 0.0001) and age (F = 9.59, P = 0.0026). By contrast, sVCAM-1 concentration was not increased in nondiabetic patients with atherosclerotic change of the carotid arteries (668 +/- 191 ng/ml; n = 36) compared with those without the atherosclerotic change (632 +/- 177 ng/ml; n = 28), and there was no correlation between sVCAM-1 level and IMT of the carotid arteries in the nondiabetic subjects. These results indicate that circulating sVCAM-1 may be a marker of atherosclerotic lesions in NIDDM patients with symptomatic and asymptomatic atherosclerosis.

Soluble adhesion molecules reflect endothelial cell activation in ischemic stroke and in carotid atherosclerosis.

Activation of endothelial cells and platelets plays an important role in the development of atherosclerosis and thrombotic disorders. Soluble adhesion molecules originating from these cells can be demonstrated in plasma. We hypothesized that elevated plasma concentrations of soluble P-selectin (sP-selectin), soluble intercellular adhesion mole-cule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) can reflect activation of endothelial cells and/or platelets in acute ischemic stroke and in previously symptomatic internal carotid artery stenosis. Plasma was sampled from patients within 2 days of acute ischemic stroke (n = 28), from patients with a previous (> 1 week) transient or persistent ischemic neurological deficit associated with stenosis of the internal carotid artery (n = 34), and from control patients without a history of vascular disease (n = 34). Concentrations of sP-selectin, sICAM-1, sVCAM-1, and sE-selectin were measured by means of an enzyme-linked immunosorbent assay. Compared with control subjects, sP-selectin and sE-selectin were significantly elevated in the acute stage of ischemic stroke (P < .0001 and P = .001, respectively) as well as in previously symptomatic carotid stenosis (P < .0001 and P = .0007). sICAM-1 and sVCAM-1 were not increased. The elevated levels of sE-selectin indicate that endothelial cell activation occurs both in the acute stage of ischemic stroke and in previously symptomatic carotid atherosclerosis. Increased sP-selectin concentrations reflect endothelial cell activation as well but may also be caused by platelet activation.

Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre‐eclampsia

To investigate the correlation between soluble forms of the intercellular adhesion molecule (sICAM-1) and vascular cell adhesion molecule (sVCAM-1) and the severity of pre-eclampsia or its possible consequences for fetal growth. Prospective observational study. Institute of Medical Genetics, University of Oslo, Department of Medical Genetics and Haematological Research Laboratory, Ullevål University Hospital; and the Department of Obstetrics and Gynaecology, The National Hospital, Oslo, Norway. Seventy-six women with normotensive pregnancies and 157 women with pre-eclampsia divided into three subgroups: mild, severe and pre-eclampsia with fetal growth retardation. ELISA-measurements of plasma sICAM-1 and sVCAM-1 were performed in a group of healthy pregnant normotensive women and three groups of women with varying degrees of pre-eclampsia. sICAM-1 concentrations were higher in the pre-eclampsia group compared with the control group, but this difference was not statistically significant. Plasma concentrations of sVCAM-1 were significantly greater (P < 0.0001) in all pre-eclampsia subgroups (835.34, 855.25 and 964.05 ng/mL) compared with the control group (667.62 ng/mL). Within the pre-eclampsia group, plasma concentration of sVCAM-1 was significantly higher in the subgroup exhibiting fetal growth retardation (P = 0.03) compared with mild pre-eclampsia. The observed increases in plasma concentrations of sVCAM-1 suggest that measurements of this adhesion molecule may be useful in monitoring pregnancies with respect to the development of pre-eclampsia or fetal growth retardation.

Assessment of soluble adhesion molecules (sICAM-1, sVCAM-1, sELAM-1) and complement cleavage products (sC4d, sC5b-9) in urine. Clinical monitoring of renal allograft recipients.

Increasing evidence exists that inducible adhesion molecules are involved in cell-mediated allograft rejection. In addition, complement activation during rejection has been described. This study investigated, whether specific molecules derived from either pathway are excreted into urine during rejection and whether they can provide useful diagnostic tools for the monitoring of renal transplant recipients. Urinary concentrations of soluble adhesion molecules (sICAM-1, sVCAM-1, sE-selectin) and of complement cleavage products (sC4d and sC5b-9), were determined by standardized ELISA in 30 normal controls and 80 samples from 49 recipients of renal allografts. In contrast to the low amounts of adhesion molecules and complement components uniformly excreted by healthy persons (group 0), marked differences were observed among allograft recipients. To prove the clinical relevance of these differences in excretion, patient samples were assigned to 5 categories according to clinical and histopathological criteria: group I--acute steroid-resistant rejection (n = 10); group II--acute steroid-sensitive rejection (n = 10); group III--chronic rejection (n = 23); group IV--stable graft function (n = 27); and group V--miscellaneous disorders (n = 10), including infections, CsA overdoses, and glomerulonephritis. Urinary levels of sICAM-1, sVCAM-1, and sC4d were significantly higher in group I compared with all other groups (P < 0.01). The difference in sICAM-1 excretion between groups III and IV also reached statistical significance (P < 0.05). Urinary concentrations of sICAM-1, sVCAM-1, and sC4d were reflective of their histological distribution in corresponding graft biopsies. None of the patients excreted E-selectin in detectable amounts. Excretion of the terminal membrane attack complex C5b-9 was not significantly associated with any diagnosis. It is concluded that for clinical purposes the combined evaluation of sICAM-1, sVCAM-1, and sC4d is most useful and can provide valuable information with regard to the severity and the type of allograft rejection.