Background-The shear stress induced by blood flow may play a pivotal role i
n the induction or prevention of atherosclerosis by changing endothelial fu
nctions. To disclose the mechanisms of this change, we prepared an endothel
ial cell (EC) cDNA library to select specific clones expressed in response
to shear stress.
Methods and Results-The mRNA of cultured confluent bovine aortic ECs (BAECs
) subjected to steady laminar shear stress (30 dyne/cm(2)) for 4 hours was
separated, and a cDNA library was prepared. Nine clones whose expressions w
ere specifically enhanced by the shear stress were selected by use of a dif
ferential hybridization method. One clone had 94% homology at the nucleotid
e sequence level to Oryctolagus cuniculus gro (GRO) mRNA and 79% homology a
t the amino acid sequence level to human GRO-beta. The GRO mRNA expression
was increased in both BAECs and human umbilical vein ECs (HUVECs) after the
ECs were subjected to high (30 dyne/cm(2)) and low (5 dyne/cm(2)) laminar
shear stress. GRO-alpha and/or -beta protein expression also increased afte
r the HUVECs and BAECs were subjected to shear stress. Because GRO protein
has been shown to function as an adhesion factor of monocytes on the surfac
e of ECs, we studied whether shear stress-induced monocyte adhesion was cau
sed by GRO protein expression on ECs. The 4-hour shear stress enhanced mono
cyte adhesion to ECs by 2.5-fold over control levels, and this enhancement
was inhibited by 53% by anti-GRO-alpha antibody.
Conclusions-The present study is the first report that shear stress induced
the expression of GRO mRNA and protein in ECs and enhanced the monocyte ad
hesion on ECs via GRO protein. Further investigations of the functions and
participation in atherogenesis of this selected clone may clarify the signi
ficance of shear stress on atherogenesis.