PMID- 8197118 OWN - NLM STAT- MEDLINE DCOM- 19940627 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 91 IP - 11 DP - 1994 May 24 TI - Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. PG - 4678-82 AB - The focal distribution of atherosclerotic lesions in the arterial tree is related to the local shear stress generated by blood flow, but the molecular basis of the atherogenic response of endothelial cells in these lesion-prone areas is still unclear. We report that shear stress mediates a biphasic response of monocyte chemotactic protein 1 (MCP-1) gene expression in vascular endothelial cells (EC). Northern blot analysis indicated that the level of MCP-1 mRNA in human umbilical vein EC (HUVEC) subjected to a shear stress of 16 dynes/cm2 (1 dyne = 10 microN) for 1.5 hr increased by 2- to 3-fold when compared with static cells. The MCP-1 gene expression decreased to the basal level at 4 hr and then declined further to become completely quiescent at 5 hr after the onset of shear. Once the gene expression was fully suppressed, it remained quiescent even after static incubation for 1.5 hr and would not respond to reshearing after this static incubation. However, if the postshearing incubation extended from 1.5 to 24 hr, the MCP-1 mRNA returned to the basal level and was then able to increase after the reapplication of shear stress. Nuclear run-on experiments showed that the shear-induced increased MCP-1 mRNA in HUVEC was regulated at the transcriptional level. By using cycloheximide, it was shown that de novo protein synthesis was not necessary for the induction of MCP-1 by shear stress. The biphasic response of MCP-1 gene expression was found in experiments in which the applied shear stress was 6, 16, or 32 dynes/cm2, and it was observed not only in HUVEC but also in HeLa cells, glioma cell lines, and skin fibroblasts. This in vitro study demonstrates that the response of MCP-1 gene to shear stress represents an immediate early gene activation and suggests that this gene is probably suppressed in EC that have been exposed to a constant shear stress. FAU - Shyy, Y J AU - Shyy YJ AD - Institute for Biomedical Engineering, University of California at San Diego, La Jolla 92093-0412. FAU - Hsieh, H J AU - Hsieh HJ FAU - Usami, S AU - Usami S FAU - Chien, S AU - Chien S LA - eng GR - HL 19454/HL/NHLBI NIH HHS/United States GR - HL 43026/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) SB - IM MH - Biomechanical Phenomena MH - Blotting, Northern MH - Cell Line MH - Chemokine CCL2 MH - Chemotactic Factors/biosynthesis/*genetics MH - Endothelium, Vascular/cytology/*metabolism MH - HeLa Cells MH - Humans MH - Protein Biosynthesis MH - RNA Processing, Post-Transcriptional MH - Transcription, Genetic PMC - PMC43851 EDAT- 1994/05/24 00:00 MHDA- 1994/05/24 00:01 PMCR- 1994/11/24 CRDT- 1994/05/24 00:00 PHST- 1994/05/24 00:00 [pubmed] PHST- 1994/05/24 00:01 [medline] PHST- 1994/05/24 00:00 [entrez] PHST- 1994/11/24 00:00 [pmc-release] AID - 10.1073/pnas.91.11.4678 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1994 May 24;91(11):4678-82. doi: 10.1073/pnas.91.11.4678.