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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1770.)
© 2001 American Heart Association, Inc.

Vascular Biology

Pulsatile Flow Regulates Monocyte Adhesion to Oxidized Lipid-Induced Endothelial Cells

Tzung K. Hsiai; Sung K. Cho; Srinivasa Reddy; Susan Hama; Mohamad Navab; Linda L. Demer; Henry M. Honda; Chih M. Ho

From the Division of Cardiology, Department of Medicine (T.K.H., H.M.H., S.R., S.H., M.N., L.L.D.), Department of Physiology (L.L.D.), and Department of Molecular and Medical Pharmacology (S.R.), UCLA School of Medicine, and the Department of Mechanical and Aerospace Engineering (T.K.H., S.K.C., C.M.H.), UCLA School of Engineering and Applied Sciences, Los Angeles, Calif.

Correspondence to Tzung K. Hsiai, MD, Division of Cardiology, 47-123 CHS, UCLA School of Medicine, Los Angeles, CA 90095-1679. E-mail thsiai{at}mednet.ucla.edu

Abstract—— 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 (/t), 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 rate (/t=293 dyne · cm^-2 · s^-1), with time-averaged shear stress=50 dyne/cm²; (2) low shear stress slew rate (/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 /t reduced monocyte binding to ox-PAPC-treated BAECs by 64±3.2% compared with static conditions, and low /t reduced monocyte binding by 31±3.4%, whereas oscillating flow increased monocyte binding by 22±1.7% (P<0.005). High /t downregulated MCP-1 expression by 33±8%, and low /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.

Key Words: shear stress • slew rate • oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine • monocyte adhesion • monocyte chemoattractant protein-1

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