Soluble ICAM-1: A marker of vascular inflammation and lifestyle

Abstract

The circulating form of a membrane-bound intercellular adhesion molecule-1 (ICAM-1), has been the source of recent debate as a candidate marker of vascular inflammation in atherosclerosis and myocardial infarction, although its increased levels were also observed in other diseases affecting the cardiovascular system, such as myocarditis, inflammatory cardiomyopathy and heart failure per se. Faulty dietary habits, a sedentary mode of life, smoking, and alcohol abuse, are factors which at least in part contribute to atherosclerosis. This paper describes the responses of sICAM-1 levels to nutrients, physical activity, smoke exposure and alcohol consumption.

Introduction

Vascular inflammation has been described in a number of diseases with different pathological backgrounds, varying in progress and prognosis. Generally, vascular involvement is characterized by an inflammatory process in the wall of a blood vessel. Inflammation may occur in vasculitis syndromes, as well as in infectious diseases.

Vascular dysfunction and inflammation develops in atherosclerosis as a consequence of abnormalities in lipid metabolism [1], which generate immune response. Stimulated by proinflammatory cytokines, leukocytes migrate across the endothelium following interaction between adhesion molecules (CAMs) expressed on endothelial cells and the appropriate receptors present on leukocytes [2], [3]. Recruitment of leukocytes into the vessel wall, foam cell formation and smooth muscle cell proliferation causes damage to the vascular walls. Several lines of evidence indicate that intercellular adhesion molecule-1 (ICAM-1, CD54) is a useful parameter when estimating the extent of atherosclerosis, since elevated ICAM-1 expression can be observed in atheromatous plaques [4], [5], [6]. The soluble intercellular adhesion molecule-1 (sICAM-1), a circulating form of a membrane-bound ICAM-1, has been a source of recent debate as a candidate marker for vascular inflammation in atherosclerosis and myocardial infarction [7], [8], although its increased levels were also observed in other diseases affecting the cardiovascular system, such as myocarditis, inflammatory cardiomyopathy and heart failure per se [9], [10], [11]. Soluble ICAM-1 fulfils enough suitable criteria to consider it a marker of vascular inflammation. Firstly, the release of circulating forms of ICAM-1 is believed to reflect ICAM-1 expression on endothelial cells [12]. Secondly, the level of soluble ICAM-1 in humans correlates with the extent of atherosclerosis [13]. Finally, it must be mentioned that sICAM-1 can be easily determined in the plasma/serum using radioimmune (RIA) or enzyme-linked immunosorbent (ELISA) assays.

ICAM-1 belongs to the immunoglobulin super-family. It is constitutively expressed at low levels on the surface of different cell lines or is inducible on their membranes with mediators of inflammation. CAM's expression on endothelial and other cells is regulated by a transcription factor NF-κB [14]. The release of ICAM-1 from these cells has been found to be inducible by several inflammatory mediators and other factors including IL-1 [15], [16], TNF-α [16], angiotensin II [17], and non-oxidised LDL [18]. It is presumably cleaved from the cell membrane by specific enzymes [19]. Soluble ICAM-1 is a 453 amino acid residue glycosylated peptide that comprises an extracellular part of ICAM-1. The molecule is composed of 5 distinct domains, stabilised by disulphide bonds. Physiologically sICAM-1 concentration in plasma or serum varies in a range of 200–300 ng/mL, however, a significant rise was observed in diseases of distinct aetiology.

Lifestyle, which includes diet, physical activity, addictions etc., is among the factors which determine health in man. Improper nutrition is known to make a contribution to obesity, atherosclerosis, increased coronary heart disease (CHD) risk, diabetes, and bowel cancer.