Role of ligand specific integrins in endothelial cell alignment and elongation induced by cyclic strain

Abstract

The mechanisms by which vascular endothelial cells (EC) sense and respond to biochemical stimuli remain to be elucidated. The aim of this study is to clarify the role of specific integrin in the morphological change induced by cyclic strain (CS) via the p38 mitogen activated protein kinase (p38 MAPK) pathway. EC were cultured on collagen-I (a ligand for α2β1) coated flexible plates and exposed to average of 15.6% CS at a frequency of 60 cycles/min in presence or absence of anti-α2 integrin antibody (anti-α2) or anti-α5 integrin antibody (anti-α5) or anti-β1 integrin antibody (anti-β1) or anti-β4 integrin antibody (anti-β4). The mean orientation angle of EC subjected to CS with anti-α2, anti-β1 and without anti-integrin antibody were 45°, 52° and 21°, respectively. The mean cell shape index [defined as (4π × cell area)/(cell perimeter)2] of EC subjected to CS with anti-α2, anti-β1 and without anti-integrin antibody were 0.63,0.72 and 0.25, respectively. Peak phosphorylation of p38 MAPK was 3.4 fold at 60min compared with static control. In contrast, phosphorylation of p38 MAPK was inhibited by anti-α2 or anti-β1 during the time course of experiment. Anti-α5 and anti-β4 did not abolish EC elongation and alignment, these antibodies had no effect on the activation of p38 MAPK. Our results indicate that ligand specific integrins play a crucial role in the morphological change via p38 MAPK pathway induced by CS.