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Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?

Journal of Human Hypertension volume 17, pages 449–453 (2003)Cite this article

It is now generally accepted that atherosclerosis is an inflammatory disease, and that the initiating factor is endothelial dysfunction.1,2 This is followed by inflammatory cell infiltration and lipid accumulation; which in turn stimulate vascular smooth muscle cell proliferation, migration and extra-cellular matrix production. Normally, the vascular endothelium resists the binding of leucocytes, presenting a barrier to their infiltration into the subendothelial layer. However, a variety of stimuli may impair endothelial function, rendering it susceptible to leucocyte adhesion, and potentially initiating atherogenesis. Similar processes are also implicated in the acute manifestations of atherosclerosis.3 The predominant mechanism in the pathogenesis of the acute coronary syndromes is atherosclerotic plaque rupture. Histological evidence confirms that this is characterised by infiltration of leucocytes.4 These release proteolytic enzymes that weaken the extracellular matrix destabilising the plaque, and increasing the risk of exposure of its thrombogenic subendothelial matrix and lipid core. Endothelial erosion, a less common but important cause of unstable atherosclerotic disease, particularly in younger patients, is also associated with dysfunction and destruction of endothelial cells.4 Once again the adhesion of leucocytes is a fundamental component of this process.

The binding of leucocytes to vascular endo-thelium is mediated by a variety of cell surface adhesion receptors–principally the selectins and integrins. The selectins are the initiators of adherence, but the binding they induce is weak, allowing leucocytes to roll along the vessel wall. This contact enables leucocyte and endothelial integrins to interact, permitting the more secure binding that precedes spreading and infiltration. The main endothelial integrin receptors are vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), which bind to leucocyte β1 (α4β1) and β2 (αLβ2 and αMβ2) integrins, respectively. Normal vascular endothelium expresses little or no VCAM-1 or ICAM-1. They are, however, induced by endothelial dysfunction, suggesting that they may represent biological ‘markers’ of atherosclerosis and might predict an increased risk of its acute manifestations. Certainly, focal endothelial VCAM-1 and ICAM-1 have been demonstrated overlying areas of early atherogenesis5,6 and within atherosclerotic plaques.7,8,9 Furthermore, mice deficient in VCAM-1 are protected against the development of atherosclerosis,10 whereas the data regarding ICAM-1 knockout mice are conflicting.10,11,12,13

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  1. Department of Cardiology, University of Aberdeen, Aberdeen, UK

    G S Hillis

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Hillis, G. Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light?. J Hum Hypertens 17, 449–453 (2003). https://doi.org/10.1038/sj.jhh.1001569

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