Elsevier

Metabolism

Volume 54, Issue 8, August 2005, Pages 1020-1026
Metabolism

Soluble adhesion molecules (sICAM-1, sVCAM-1) and selectins (sE selectin, sP selectin, sL selectin) levels in children and adolescents with obesity, hypertension, and diabetes

https://doi.org/10.1016/j.metabol.2005.03.004Get rights and content

Abstract

The attachment of monocytes and lymphocytes to endothelial cells, which initiates atherosclerosis, arises under the influence of adhesion molecules. The preclinical phase of this disease lasts many decades, and this provides an opportunity for the presymptomatic detection of high-risk subjects. We evaluated levels of the adhesion molecules: sICAM-1 (soluble intercellular adhesion molecule 1), sVCAM-1 (soluble vascular adhesion molecule 1), sE selectin, sP selectin, and sL selectin in children with atherosclerosis risk factors (n = 123, mean age 15.1 years) (obese [n = 17], hypertensive [n = 25], obese with hypertension [n = 30], type 1 diabetic [n = 51]). Twenty-seven healthy children formed the control group, mean age 15.2 years. sICAM-1 was higher in the study group compared with control (314.1 ± 61 vs 264.9 ± 55 ng/mL, P < .01). The same was found for sVCAM-1 (513.7 ± 187 vs 407.9 ± 76 ng/mL, P < .05) and E selectin (86.04 ± 33.6 vs 62.1 ± 20.3 ng/mL, P < .01). sP-selectin and sL-selectin levels were not different compared with controls. E selectin correlated with body mass index (BMI; r = 0.18, P = .03), total cholesterol (r = 0.2, P = .016), and triglycerides (r = 0.22, P = .008). sICAM-1 correlated with BMI (r = 0.19, P = .019) and systolic blood pressure (r = 0.13, P = .045). In multiple linear regression analysis, sE selectin was found to be associated with triglycerides (R2 = 0.29, P = .045), sICAM-1 dependent on BMI (R2 = 0.58, P = .047), and sVCAM-1 dependent on total cholesterol (R2 = 0.51, P = .006). Elevated concentrations of sICAM-1, sVCAM-1, and E selectin were found in obese, hypertensive, and diabetic children. We conclude that endothelial activation appears in these children, and adhesion molecules are related to the earliest stages of atherosclerosis.

Introduction

Vascular endothelium is currently being regarded as not a passive barrier between flowing blood and the vascular wall, but as a highly specialized metabolically active tissue [1], [2]. The most important changes that occur during the activation of endothelial cells, under the stimulatory influence of various factors, consist of an increased expression of adhesion molecules and selectins, whose soluble forms can be detected in blood. This increased expression leads to the rolling, activation, and firm adhesion of leukocytes to the endothelium [3], [4]. Although adhesion molecules are vital for the normal development and function of the heart and blood vessels, they have also been implicated in the pathogenesis of cardiovascular disease [5], [6], [7].

Damage of the endothelium in the form of its desquamation is not an essential component of and is typically absent in the first stage of the atherosclerotic process. Attachment of monocytes and lymphocytes to endothelial cells, which initiates the process of atherosclerosis, arises under the influence of cellular adhesion molecules (CAMs) [7]. Binding of these cells to the endothelium requires the interaction of integrin on the surface of leukocytes with intercellular adhesion molecule 1 (ICAM-1), VCAM-1 (vascular adhesion molecule 1), and selectins on the endothelium [6]. By losing its protective properties and allowing the unopposed action of atherogenic factors on the vessel wall, dysfunctional endothelium is a major promoter of atherosclerosis [1]. After transmigration into the vessel wall, leukocytes release various bioactive molecules, which initiate the development of lipid deposits and foam cells as well as proliferation of smooth muscle cells [7], [8].

Although the main clinical consequences of atherosclerosis such as myocardial infarction or stroke usually occur in adults, the atherogenic process actually begins during childhood, the time of onset of fatty infiltration of the vasculature [9]. This preclinical phase lasts many decades, and this pattern of the disease provides an opportunity for the presymptomatic detection, identification of high-risk subjects, and the application of appropriate prevention strategies [10], [11].

Risk factors for atherosclerosis appear during childhood and are already by this time associated with atherosclerotic changes in vessel walls. The process of atherosclerosis is accelerated in children in whom multiple risk factors for the disease are present [12]. There is a great need to find and evaluate noninvasive methods to ensure a reliable detection of high-risk young subjects during the long presymptomatic phase of the disease, during which such endothelial changes are entirely reversible [2], [10], [13].

The aim of the study was to evaluate the concentrations of soluble forms of adhesion molecules ICAM-1 and VCAM-1 and selectins E selectin, P selectin, and L selectin in children and adolescents with a presence of atherosclerosis risk factors (obesity, hypertension, and diabetes), and to compare these with healthy controls, as well as to find out the correlations between these molecules and studied parameters such as lipid levels, blood pressure values, and body mass index (BMI). We also wanted to discover if evaluation of concentration of any of these molecules can be helpful in detection of endothelial activation in identification of high-risk young patients.

Section snippets

Subjects

The study consisted of patients of the 2nd Department of Children's Diseases of the Medical University of Bialystok Poland and its related outpatient clinics for diabetes, cardiology, and endocrinology. In total, 123 (69 boys and 54 girls) children and adolescents were included, with the mean age being 15.1 ± 3.3 years (age 8-20 years). The group was divided according to their diagnosis. Group A (n = 17) consists of obese children; B (n = 30) consists of children diagnosed with obesity and

Results

Table 1 summarizes the results of routine lipid analysis. Total cholesterol was higher in the study group compared with controls (4.54 ± 0.8 vs 4.15 ± 0.6 mmol/L, P < .05). The highest levels were found in groups of obese and hypertensive children (group B), 4.75 ± 0.8 mmol/L (P < .01), and diabetic children (group D), 4.7 ± 0.8 mmol/L (P < .01). Triglyceride levels were significantly higher in all the selected groups of patients. The mean level was 1.33 ± 0.7 mmol/L in the whole study group vs

Discussion

Our study showed increased concentrations of the adhesion molecules sICAM-1, sVCAM-1, and E selectin in children and adolescents burdened with risk factors for atherosclerosis such as obesity, hypertension, and diabetes. The highest concentrations of these molecules appeared in obese children with coexisting hypertension, whereas lean hypertensive children showed only higher concentrations of the molecule sICAM-1. Current literature does not show much research concerning adhesion molecules or

Conclusions

Elevated levels of sICAM-1, sVCAM-1, and E selectin were found in obese, hypertensive, and diabetic children and adolescents. We conclude that endothelium activation appears in these children and that adhesion molecules are related to the earliest stages of atherosclerosis. Based on our findings and the reports of other studies, it is difficult to definitively determine the role of the various adhesins during the pathogenesis of atherosclerosis and the usefulness of assessing their serum

Acknowledgment

This work was supported by the State Committee for Scientific Research grant no. 4 PO 5E 072 19.

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