Shear Stress Inhibits Smooth Muscle Cell–Induced Inflammatory Gene Expression in Endothelial Cells: Role of NF-κB

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 25; no. 5; pp. 963 - 969
• Main Authors: Chiu, Jeng-Jiann, Chen, Li-Jing, Chang, Shun-Fu, Lee, Pei-Ling, Lee, Chih-I, Tsai, Min-Chien, Lee, Ding-Yu, Hsieh, Hsing-Pang, Usami, Shunichi, Chien, Shu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.05.2005; Hagerstown, MD Lippincott
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Medical sciences; Vertebrates: cardiovascular system; Endothelial cell; endothelial cells; Cardiovascular disease; Smooth muscle; cDNA microarray; Gene expression; Vascular disease; smooth muscle cells; coculture; Complementary DNA; Atherosclerosis; Shear stress; Inflammatory cell
• DOI: 10.1161/01.ATV.0000159703.43374.19
• ISSN: 1079-5642

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/cm) 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-κB (NF-κB) activation by the p65-antisense, lactacystin, and N-acetyl-cysteine blocked the coculture-induced EC expression of proinflammatory genes, indicating that the NF-κB 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-κB recruitment to selected target promoters. Shear stress inhibited the SMC coculture-induced NF-κB 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.