Abstract 132: Simulated Intraplaque Hemorrhage Stimulates Plaque Progression in an Animal Model
Intraplaque hemorrhage (IPH) is a feature of advanced plaques and a risk factor for clinical events. Several studies have demonstrated a link between carotid IPH and subsequent cerebrovascular events. Deposited RBCs contribute ingredients likely to promote plaque instability.
In this study, a catheter-based approach was used for intramural injection of RBCs into atherosclerotic plaques. We explored the hypothesis that an animal model of atherosclerosis demonstrates increased macrophage infiltration and neovascularization in plaques injected with RBCs.
Rabbits (n=4) were administered high cholesterol diet starting 2 weeks prior to endothelial denudation. Five weeks after denudation, a microinfusion catheter with a balloon-actuated microneedle delivered 70-100 μl of RBC and iodinated contrast mixture at multiple sites along the aorta. X-ray fluoroscopy and CT identified plaque injection sites and aortas were harvested for histopathology 5 weeks later.
Only sections from plaque injection sites (n=14) were positive for Perl’s iron stain. In the 3 aortas analyzed with immunohistochemistry (1 excluded due to plaque variability), plaque macrophage area proportion was significantly higher in plaque injection sites vs. non-injected vessel sections. Increase in plaque neovessel density was not significant. In conclusion, intraplaque deposition of RBCs in the atherosclerotic rabbit aorta increases measures of plaque instability.
Micrographs show Perl’s iron (a), macrophage (b), and neovessel (c) staining in an RBC-injected plaque. Scale bars represent 250 μm. Mean macrophage proportion and microvessel density and associated SEM are shown in bar graphs.
- © 2013 by American Heart Association, Inc.