Cyclic Strain Enhances Adhesion of Monocytes to Endothelial Cells by Increasing Intercellular Adhesion Molecule-1 Expression

Abstract

Since endothelial cells are constantly subjected to pressure-induced strain, we examined how cyclic strain affects the expression of intercellular adhesion molecule-1 (ICAM-1). Endothelial cells grown on a flexible membrane base were deformed by different sinusoidal negative pressures (-10, -15, or -20 kPa) to produce an average strain of 9%, 11%, and 12%, respectively, for various times. The release of the soluble form of ICAM-1 from strained endothelial cells increased in a time- and strain-dependent manner. Using flow cytometric analysis, we showed the induction of ICAM-1 expression on the endothelial cell surface to depend on both time and the amount of strain. Northern blot analysis revealed a sustained, approximately 1.8-fold increase in ICAM-1 mRNA levels in 11% strained cells. Strain-induced expression of ICAM-1 correlated with a strain-dependent increase in adhesion of monocytic cells to strained cells. This increase in monocytic cell adhesion could be partially inhibited by pretreatment of strained cells with antibody to ICAM-1. These results indicate that mechanical strain can stimulate the expression of ICAM-1 by endothelial cells and thus contribute to the increased adhesion of monocytes to strained cells. Such strain-induced expression of ICAM-1 may contribute to the trapping of monocytes on local vascular walls where strain is high and to the initiation of atherogenesis, thus providing a possible link between hypertension and atherogenesis.