Abstract 15126: Adventitial Plaque Microvessels in Apoe-/- Mice Show Angiogenic Activity, Active Perfusion, Increased Leukocyte Adhesion and Permeability, and Reduced Blood Flow Velocity
Background Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization. We hypothesized that plaque microvessels exhibit specific functional characteristics, contributing to plaque development. Here, we studied functional properties of adventitial plaque microvessels in mice in vivo.
Methods Carotid arteries from aged ApoE-/- mice (>40 wks; n=45), age-matched C57Bl/6 mice (n=20) and young ApoE-/- mice (16 wks; n=8) were imaged using in vivo multiphoton laser scanning microscopy. Mice were injected with fluorescently labeled probes to label the vascular endothelium (anti-CD31) and assess angiogenic properties (cNGR). Fluorescently labeled dextrans, leukocytes and platelets allowed assessment of microvessel perfusion, permeability and blood flow velocity. Also, leukocyte adhesion to and extravasation from adventitial microvessels were determined.
Results Adventitial microvessels were found in close proximity of the atherosclerotic plaque in 87% of aged ApoE-/- mice, while absent in younger ApoE-/- and aged C57Bl/6 mice. Median diameter was 18.5 ± 0.4 and 5.9 ± 0.05 μm for 1st and 2nd order microvessels. In vivo imaging of adventitial microvessels showed angiogenic activity (cNGR). Co-injection of FITC-dextran and anti-CD31 confirmed active perfusion, and revealed increased permeability for 70 kDa, but not 150 kDa dextran. Blood flow velocity in adventitial microvessels was 0.14 ± 0.01 mm/s (mean ± SEM), representing a 50% lower flow velocity compared to control microvessels of equal diameter (0.30 ± 0.01 mm/s; p<0.005). Both adhesion (1.25 ± 0.26 vs. 0.22 ± 0.14 x10-2 cells/mm2/min, p<0.05) and extravasation (1.75 ± 0.37 vs. 0.29 ± 0.24 x10-2cells/mm2/min, p<0.05) of leukocytes were increased in adventitial microvessels compared to control microvessels.
Conclusion Plaques of aged ApoE-/- mice showed adventitial microvessels, which were angiogenically active and, albeit lowly, perfused. These microvessels showed increased permeability, decreased blood flow and flow velocity, yet increased leukocyte adhesion and extravasation. The increased leakiness and extravasation of leukocytes suggest an important role for adventitial microvessels in contributing to plaque progression.
- © 2011 by American Heart Association, Inc.