Shear Flow Field Of Ultrasound And Endothelial Cell Adhesion Regulatory Rate

The early stages of atherosclerosis are characterized by increased endothelial cell surface expression of leukocyte adhesion molecules. Ultrasound detection of targeted microbubbles might provide a modality to noninvasively assess the functional status of the vascular endothelial cell. However, the law of adhesion between targeted microbubbles with different surface density of targeted antibody and endothelial cells is not well understood. Lipid-based perfluorobutane-filled microbubbles targeting to VCAM-1, which was overexpressed in the early stage of atherosclerosis and inflammation, was synthesized by multi-step avidin-biotin bridging chemistry. HUVEC-CS cells, a subline of human umbilical vein endothelial cells, were exposed to microbubbles with various anti-VCAM-1 coverage percentage of 22.2%, 33.2%, 63.3% and100% under the wall shear stresses of 2 and 5 dynes/cm2 in a parallel plate perfusion chamber. HUVEC-CS cells were activated by lipopolysaccharide (LPS). It was found that VCAM-1 expression was up-regulated in LPS-stimulated HUVECs. The number of microbubble adhesion to HUVEC-CS monolayer was dependent on the anit-VCAM-1 ligand density and the exposed shear stress. The adhesed microbubbles were increased by 34-fold and 50-fold for anti-VCAM-1 coverage percentage of 100% when compared with control in 2 dynes/cm2 and 5 dynes/cm2, respectively. It was also demonstrated that the adhesed microbubbles decreased by more than 3-fold at the same anti-VCAM-1 coverage percentage when compared the two shear stresses. It indicated that the novel targeted microbubbles have the potential in the early assessment and diagnosis for vascular diseases.