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
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.
References (43)
Endothelial dysfunction: does it matter? Is it reversible?
J Am Coll Cardiol
(1997)- et al.
Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study)
Am J Cardiol
(1992) - et al.
Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes
Atherosclerosis
(2003) - et al.
Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians
Atherosclerosis
(2002) - et al.
Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men
Lancet
(1998) - et al.
Circulating E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in men with coronary artery disease assessed by angiography and disturbances of carbohydrate metabolism
Metabolism
(2002) - et al.
Hypothesis: is soluble P-selectin a new marker of platelet activation?
Atherosclerosis
(1997) - et al.
Endothelial function. From vascular biology to clinical applications
Am J Cardiol
(2002) - et al.
Endothelial cell activation. A central pathophysiological process
BMJ
(1998) - et al.
Endothelial adhesion molecules in health and disease
Pathol Biol (Paris)
(1998)
The endothelium in atherothrombotic disease: assessment of function, mechanisms and clinical implications
Blood Coagul Fibrinolysis
Cell adhesion molecules in cardiovascular disease: a clinical perspective
Heart
Atherosclerosis—an inflammatory disease
N Engl J Med
Changing concepts of atherogenesis
J Intern Med
Noninvasive detection of atherosclerosis
N Engl J Med
The role of integrin-mediated cell adhesion in health and disease: integrin-based therapy in clinical medicine
Ann Intern Med
Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study
N Engl J Med
Evaluating novel cardiovascular risk factors: can we better predict heart attacks?
Ann Intern Med
Somatic development indices in children and youth of Warsaw
Med Wieku Rozwoj
Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents
Pediatrics
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
Diabetes Care
Cited by (163)
Rheological and interface adhesive properties of osteoarthritic synovial fluids
2022, BiotribologyCitation Excerpt :For instance, the shorter hydrophobic chain length of SAPLs in osteoarthritic SFs [97,98] might diminish lubrication due to the reduced adsorption on the AC surface [99]. Moreover, obesity could cause an inflammatory environment in the joints [79], impelling an increase in cell-adhesion molecules like the E-selectin and the Intercellular Adhesion Molecule 1 (ICAM-1) [100,101]. Averaged adhesion energy of the SF samples collected from female patients is 8–67% lower than those from male patients (Fig. 9).
Microvascular basis of cognitive impairment in type 1 diabetes
2022, Pharmacology and Therapeutics