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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:963.)
© 2005 American Heart Association, Inc.

Vascular Biology

Shear Stress Inhibits Smooth Muscle Cell–Induced Inflammatory Gene Expression in Endothelial Cells

Role of NF-B

Jeng-Jiann Chiu; Li-Jing Chen; Shun-Fu Chang; Pei-Ling Lee; Chih-I Lee; Min-Chien Tsai; Ding-Yu Lee; Hsing-Pang Hsieh; Shunichi Usami; Shu Chien

From the Division of Medical Engineering Research (J.-J.C., L.-J.C., S.-F.C., P.-L.L., C.-I.L., M.-C.T., D.-Y.L.), National Health Research Institutes, Miaoli, Taiwan; the Institute of Biomedical Engineering (J.-J.C.), National Yang-Ming University, Taipei, Taiwan; and the Division of Biotechnology and Pharmaceutical Research (H.-P.H.), National Health Research Institutes, Miaoli, Taiwan; and the Departments of Bioengineering Medicine and Whitaker Institute of Biomedical Engineering (S.U., S.C.), University of California San Diego, La Jolla, Calif.

Correspondence to Jeng-Jiann Chiu, PhD, Division of Medical Engineering Research, National Health Research Institutes, Miaoli 350, Taiwan, Republic of China. E-mail jjchiu{at}nhri.org.tw

Objectives— Vascular endothelial cells (ECs) are influenced by shear stress and neighboring smooth muscle cells (SMCs). We investigated the inflammation-relevant gene expression in EC/SMC cocultures under static condition and in response to shear stress.

Materials and Methods— Under static condition, DNA microarrays and reverse-transcription polymerase chain reaction identified 23 inflammation-relevant genes in ECs whose expression was significantly affected by coculture with SMCs, with 18 upregulated and 5 downregulated. Application of shear stress (12 dynes/cm²) to the EC side of the coculture for 6 hours inhibited most of the proinflammatory gene expressions in ECs induced by coculture with SMCs. Inhibition of nuclear factor-B (NF-B) activation by the p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced EC expression of proinflammatory genes, indicating that the NF-B binding sites in the promoters of these genes play a significant role in their expression as a result of coculture with SMCs. Chromatin immunoprecipitation assays demonstrated the in vivo regulation of NF-B recruitment to selected target promoters. Shear stress inhibited the SMC coculture-induced NF-B activation in ECs and monocytic THP-1 cell adhesion to ECs.

Conclusions— Our findings suggest that shear stress plays an inhibitory role in the proinflammatory gene expression in ECs located in close proximity to SMCs.

ECs are influenced by shear stress and SMCs. DNA microarrays showed increased proinflammatory gene expressions in ECs by static SMC coculture. Shear stress inhibits these coculture-induced expressions. NF-B is involved in these coculture and shear stress modulations of gene expressions. Our results suggest shear stress as a protective regulator against inflammation.

Key Words: cDNA microarray • coculture • endothelial cells • shear stress • smooth muscle cells

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