Pulsatile flow regulates monocyte adhesion to oxidized lipid-induced endothelial cells.
Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC), a component of minimally modified low density lipoprotein, induces monocyte adhesion to endothelial cells. It is not known whether the upstroke slopes of pulsatile flow, defined as shear stress slew rates (tau(r)/tauT)), can regulate monocyte binding to ox-PAPC-treated bovine aortic endothelial cells (BAECs). At 60 cycles per minute, ox-PAPC-treated BAECs were exposed to 3 conditions representing known vascular conditions: (1) high shear stress slew rates (tau(r)/tau(T)=293 dyne. cm(-2). s(-1)), with time-averaged shear stress=50 dyne/cm(2); (2) low shear stress slew rate (tau(r)/tau(t)=71 dyne. cm(-2). s(-1)), with identical time-averaged shear stress; and (3) reversing oscillating flow (0+/-2.6 mm Hg). Reverse transcription-polymerase chain reaction and quantification were performed for monocyte chemoattractant protein-1 (MCP-1) mRNA expression. High tau(r)/tau(t) reduced monocyte binding to ox-PAPC-treated BAECs by 64+/-3.2% compared with static conditions, and low tau(r)/tau(t) reduced monocyte binding by 31+/-3.4%, whereas oscillating flow increased monocyte binding by 22+/-1.7% (P<0.005). High partial tau(r)/tau(t) downregulated MCP-1 expression by 33+/-8%, and low partial tau(r)/tau(t) downregulated MCP-1 expression by 15+/-4%, but oscillating flow upregulated MCP-1 by 13+/-5%. These results suggest that shear stress slew rates regulate monocyte binding by modulating the expression of a potent monocyte chemoattractant.
Hsiai
T K
TK
Division of Cardiology, Department of Medicine, UCLA School of Medicine, UCLA School of Engineering and Applied Sciences, Los Angeles, California, USA. thsiai@mednet.ucla.edu
Cho
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Reddy
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Hama
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Navab
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Demer
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Honda
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D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013314:Stress, Mechanical
D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein