Effects of disturbed flow on endothelial cell function: Pathogenic implications of modified leukocyte recruitment

Article type: Research Article

Authors: Matharu, Nick M. | Rainger, G. Ed | Vohra, Rajiv | Nash, Gerard B.

Affiliations: Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham, UK

Note: [] Address for correspondence: Prof. G.B. Nash, Department of Physiology, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK. Tel.: +44 121 414 3670; Fax: +44 121 414 6919; E-mail: g.nash@bham.ac.uk.

Abstract: Numerous studies have shown that intracellular signalling, transcription factor activation and gene expression in endothelial cells are modulated by the magnitude and patterns of shear stress to which they are exposed. Although these responses suggest that the haemodynamic environment will consequently modulate the ability of the endothelial cells to support leukocyte recruitment as part of an inflammatory response, direct evidence is quite sparse. It seems that disturbances of flow (such as local spatial or temporal variation or sudden cessation) are likely to be pathogenic co-factors, combined with mediators such as cytokines, oxidised lipids or hypoxia, in conditions such as atherosclerosis, post-surgical intimal hyperplasia and ischaemia/reperfusion injury. In fact there have been few experimental investigations of these scenarios that include measurement of leukocyte adhesion and migration. We recently demonstrated that the level of steady shear to which EC are exposed has a powerful effect on their ability to support cytokine-induced leukocyte adhesion and migration. However, more combined studies of flow and agonist-mediated responses, with functional readouts, appear necessary if we are to develop a better understanding of the mechanisms pre-disposing to vascular inflammatory responses and pathology.

Journal: Biorheology, vol. 43, no. 1, pp. 31-44, 2006