CYCLIC STRAIN-INDUCED REACTIVE OXYGEN SPECIES INVOLVED IN ICAM-1 GENEINDUCTION IN ENDOTHELIAL-CELLS

Vascular endothelial cells (ECs) are constantly subjected to pressure- induced strain. We have previously demonstrated that strain can induce intercellular adhesion molecule-1 (ICAM-1) expression in ECs. The mol ecular mechanisms of gene induction by strain, however, remain unclear . Recent evidence suggests that intracellular reactive oxygen species (ROS) may act as second messengers. The potential role of ROS in strai n-induced ICAM-1 expression was examined. ECs grown on a flexible memb rane base were deformed with various sinusoidal negative pressures to produce an average strain of 12%. Cyclic strain induced an increase in intracellular ROS measured by fluorescent intensity oi dichlorofluore scein formed after peroxidation. Maximal levels of ROS were seen after 30 minutes. Levels subsequently decreased but remained elevated compa red with unstrained groups. Concomitantly, a sustained increase of H2O 2 decomposition activity was observed in strained ECs. Both ROS and H2 O2 decomposition activity returned to basal levels after removal of th e strain. ECs treated with an antioxidant (N-acetylcysteine or catalas e) inhibited strain-induced ROS generation and ICAM-1 mRNA levels foll owed by decreased ICAM-1 expression on EC surfaces, This inhibition ma y account for the reduced monocytic cell adhesion in antioxidant-treat ed ECs but not in strained controls. Our findings indicate that cyclic strain-induced monocyte adhesion to ECs is mediated, at least in part , by an increase of ICAM-1 gene expression via the elevation of ROS le vels in strained ECs. Our results support the importance of intracellu lar-ROS in the modulation of hemodynamic force-induced endothelial res ponses.