Pulsatile flow regulates monocyte adhesion to oxidized lipid-induced endothelial cells

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