Abstract 11710: High Fat Diet-Induced Leukocyte Recruitment to Femoral Artery was Compromised in E-Selectin Knockout Mice
Background: Dyslipidemia and chronic inflammation plays crucial roles in atherosclerosis. E-selectin, a member of selectin family of adhesion molecules has been shown to participate in vascular inflammation in vitro and in vivo. Although its role in small arteries and venules has been reported, no prior studies examined a contribution of E-selectin. The aim of this study is to demonstrate whether E-selectin plays a role in vascular inflammation induced by high fat diet in vivo.
Methods and Results: E-selectin knockout (E-null) mice in C57BL/6 background and their wild type littermates were fed high fat diet (HF; 20% fat, 1.25 % cholesterol) or normal chow diet (NC) for 2 weeks and leukocytes recruitment in the femoral artery was observed using an intravital microscopy. HF induced significantly more leukocyte recruitment when compared to those fed NC in the absence of mechanical injury (HF, 3.4±0.63/10-2mm2vessel surface; NC, 0±0; p < 0.01; n=10). However, HF failed to induce leukocytes accumulation in E-null mice (0.5±0.28, p<0.05 vs wild-type with HF, n=10). Real-time PCR analysis revealed that the expression levels of ICAM-1 and VCAM-1 in these vasculatures were upregulated in wild-type which was abolished in E-null mice. Flow-cytometric analysis exhibited that HF upregulated CD11b in granulocytes from wild-type which was not changed in E-null mice. The oxidative stress in leukocytes also reduced in E-null mice when compared to wild-type.
Conclusion: We identified that (1)high fat diet as short as 2 weeks induced leukocyte recruitment in the femoral artery without prior mechanical injury.(2) The Observed high fat diet-induced leukocyte recruitment was significantly abolished in E-null mice. Our findings may point a previously unrecognized role for E-selectin in vascular inflammation induced by metabolic disorders.
- © 2011 by American Heart Association, Inc.