Inflammatory monocyte response due to altered wall shear stress in an isolated femoral artery model.

Abstract

Arteriogenesis (collateral formation) is accompanied by a pro-inflammatory state that may be related to the wall shear stress (WSS) within the neo-collateral vessels. Examining the pro-inflammatory component in situ or in vivo is complex. In an ex vivo mouse femoral artery perfusion model, we examined the effect of wall shear stress on pro-arteriogenic inflammatory markers and monocyte adhesion. In a femoral artery model with defined pulsatile flow, WSS was controlled (at physiological stress, 1.4×, and 2× physiological stress) during a 24 h perfusion before gene expression levels and monocyte adhesion were assessed. Significant upregulation of expression was found for the cytokine TNFα, adhesion molecule ICAM-1, growth factor TGFβ, and the transcription factor Egr-1 at varying levels of increased WSS compared to physiological control. Further, trends toward upregulation were found for FGF-2, the cytokine MCP-1 and adhesion molecules VCAM-1 and P-selectin with increased WSS. Finally, monocytes adhesion increased in response to increased WSS. We have developed a murine femoral artery model for studying changes in WSS ex vivo and show that the artery responds by upregulating inflammatory cytokines, adhesion molecules and growth factors consistent with previous in vivo findings.