Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

The focal establishment of atherosclerotic lesions in distinct segments of arterial vessels exposed to perturbed (low shear, non-laminar, pulsatile), blood flow (PF) is preceded by the upregulation of endothelial cell (EC) adhesion molecules, such as Vascular Cell Adhesion Molecule-1 (VCAM-1) in these sites of 'atherosclerotic predilection'. To test the hypothesis that low-shear PF conditions activate the expression of adhesion molecules on cultured EC's, we exposed human aortic EC in specially designed flow/cell culture chambers to PF (0.01 - 1.5 dynes/cm2, 100 ml/min) and measured the expression of VCAM-1 using a whole cell ELISA. In contrast to the well-studied downregulation of VCAM-1 in EC exposed to laminar shear stress, exposure for 5 hours to PF resulted in a > 7 fold upregulation of VCAM-1, which was abrogated by antioxidants (PDTC, NAC). PF activated distinct cellular signaling pathways, such as the MAPK cascade (erk-1/2), as well as integrin-mediated signaling (FAK and paxillin). Using electrophoretic mobility shift assays, we failed to detect PF-mediated enhanced nuclear translocation of the redox-sensitive transcription factors NF-kappaB and AP-1. This result is surprising, since both these transcription factors are activated by laminar flow. By contrast, exposure to PF resulted in the upregulation of two other transcription factors, SP-1 and EGR-1. These results suggest that exposure of cultured endothelial cells to PF can mimic early manifestations of atherosclerotic lesions, such as the upregulation of VCAM-1.

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Presentation Number SAlelkes0243
Keywords: endothelial cells, mechanical forces, VCAM-1, oxidative stress, atherosclerosis