Vascular endothelial cells (ECs) are constantly subjected to blood flow-induced shear stress and the influences of neighboring smooth muscle cells (SMCs). We examined the gene expression in EC/SMC coculture under static condition and in response to shear stress. Under static coculture condition, DNA microarray technology led to the identification of 18 inflammation-relevant genes with significantly increased expression in ECs cocultured with SMCs and 5 inflammation-relevant genes with decreased expression, as compared with the control monocultured ECs. The microarray results were confirmed by reverse-transcription polymerase chain reaction analysis for these genes. SMCs were less responsive than ECs in their cocultures in alterations of their inflammation-relevant gene expression. The alterations in expression of inflammation-relevant genes in ECs cocultured with SMCs were not observed when ECs were cocultured with fibroblasts. The application of shear stress (12 dynes/cm2) to the EC side of the EC/SMC coculture for 6 h inhibited most of the inflammation-relevant gene expressions in ECs induced by coculture with SMCs. Moreover, shear stress inhibited the increases in monocyte adhesiveness of ECs cocultured with SMCs. Our findings support the hypothesis that shear stress acts as a negative regulator for inflammation-relevant gene expression in ECs located in close proximity to SMCs, thereby serving anti-inflammatory and atheroprotective functions in vascular biology.
