Abstract 656: Increasing Leukocyte Migration in Post-capillary Venules Correlates with the Progression of Atherosclerosis in ApoE Deficient Mice.
Atherosclerosis is a vascular disease that progresses gradually with age and affects the normal supply of arterial blood to tissues. The accumulation of inflammatory leukocytes within atherosclerotic lesions is now recognized as an important factor contributing to blood vessel narrowing. Several adhesion interactions are critical for recruitment of inflammatory leukocytes into the growing plaque. Recently, cell surface adhesion receptors that allow the interactions between leukocytes, platelets and the arterial wall in atherosclerosis-prone animals have been characterized1. In the present study we analyzed adhesive interactions between leukocytes and post-capillary venules of the cremaster muscle of various aged ApoE deficient mice. Using intravital microscopy we demonstrated that there is no difference in the rolling flux in ApoE deficient 6-week-old mice (30.4 ± 10.3 cells/min) and wild type control animals (42.6 ± 14 cells/min). The number of firmly adherent cells was also similar in 6 week old ApoE−/− (3.2 ± 0.3 cells/100 μm) and WT mice (2.8 ± 0.2 cells/100 μm). In contrast, the rolling flux in post-capillary venules of the mouse cremaster muscle was significantly increased in 6-month-old ApoE−/− mice (56 ± 14.6 cells/min) as compared to age-matched control animals (32 ± 7.7 cells/min). Strikingly, the number of leukocytes firmly adherent to the vessel wall was significantly elevated in ApoE null mice (8.8 ± 2.1 cells/100 μm in ApoE−/− versus 1.9 ± 0.2 cells/100 μm in WT control). Furthermore, older ApoE deficient, but not older control animals, had a large number of actively extravasating cells, suggesting an enhanced chemotactic activity of leukocytes. These results indicate that during the progression of atherosclerosis, systemic inflammation dramatically augments the pro-adhesive capacity of the venous endothelium and this coincides with increased leukocyte migration. Therefore, the use of intravital microscopy to view leukocyte interactions at vessels remote from the coronary artery, may provide a new methodology to help assess atherothrombotic risk.