Abstract 16744: Identification of Atherosclerotic Plaque Evolution by Imaging Cell Death
Introduction: As a consequence of inflammatory cellular infiltrates in atherosclerotic plaques, chemokines and cytokines promote a cell death cascade that contributes to plaques destabilization and rupture. This study was designed to exploit the evolution of cell death, including apoptosis and early necrosis, in atherosclerosis using 99mTc-duramycin (99mTc-DUR) targeting externalized phosphatidylethanolamine of the cell membrane.
Methods: Atherosclerosis was induced in Apolipoprotein E-Deficient (ApoE-/-) mice by feeding an atherogenic diet. Using a small-animal SPECT imager, three groups of ApoE-/- mice (n=6 each) were imaged at 2 h after 37-48 MBq 99mTc-DUR injection and euthanized at 15, 20, and 40 weeks of age (G-15, G-20, and G-40). The mice in G-40 were repeatedly imaged at three time-points before sacrifice. Age-matched wild-type mice (Apo-E+/+) were studied as controls. The aortas and other large arteries of all mice were harvested for postmortem analyses.
Results: SPECT and autoradiograph images showed that 99mTc-DUR uptake was invisible or barely visible in the aortas and brachiocephalic arteries of the G-15 mice, became detectable in the G-20, and clearly visualizable in the G-40. The ex vivo radioactive ratios of atherosclerotic aortic arches to non-plaque segments in G-40 (5.1±0.86) was significantly higher than that in G-20 (2.2±0.23) and G-15 (1.2±0.14) (P<0.01). No vascular 99mTc-DUR uptake was observed in the controls. Histological analysis indicated that there were intermediate lesions containing foam cells in the aortas of G-15 and fibrous plaques in G-20 and G-40 aortas. The G-40 mice exhibited more advanced plaque features, including extensive inflammatory infiltration, cell death, necrotic core, hemorrhage, and thinner fibrous cap (< 65 μm thick). The increased aortic 99mTc-DUR uptake correlated with upregulated measurements of plaque inflammation and cell death, including IL-1β expression, macrophage recruitments, and cell apoptosis by immunohistochemical staining and TUNEL assay.
Conclusions: Increased aortic 99mTc-DUR uptake was demonstrated during plaque evolution in atherosclerotic ApoE-/- mice, suggesting that cell death imaging may be capable of discriminating vulnerable from stable plaques.
Author Disclosures: C. Barber: None. B.T. Larson: None. B.D. Gray: Employment; Significant; Employee. K.Y. Pak: Employment; Significant; Employee. Z. Liu: None.
- © 2016 by American Heart Association, Inc.