Abstract 9624: Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of Apoe-/- Mice: Molecular Imaging with 14C-FDG and 99mTc-annexin A5
Background: Although irbesartan, an angiotensin II subtype 1 receptor blocker, reportedly can suppress the progression of atherosclerosis, the mechanisms of the therapeutic effects remain unclear. FDG and annexin A5 are two promising molecular probes that can be used to image inflammation and apoptosis, respectively.
Objectives: To clarify the relationship between the therapeutic effects of irbesartan and the inflammatory and apoptotic reactions in atherosclerotic plaques, using FDG and annexin A5.
Methods: Female apoE−/− mice were administered a diet containing irbesartan (50 mg/kg/day) for 12 weeks. After 1 week of discontinuation of the treatment, the mice (n=11) were coinjected with 14C-FDG and 99mTc-annexin A5, and the cryostat sections of aortic root were prepared 2 h after the injection. The sections were used for dual-tracer autoradiography, and the uptake levels of 14C-FDG and 99mTc-annexin A5 in the plaques were evaluated (%ID×kg). Histological examination was performed with Mac-2 (macrophage infiltration), TUNEL (apoptosis), Movat's pentachrome (plaque size), and Oil Red O (lipid deposition) staining methods on serial sections. The same experiments were performed as control with age-matched mice on irbesartan-free diet (n=11).
Results: Irbesartan treatment significantly (p<0.05) reduced the 14C-FDG and 99mTc-annexin A5 uptake levels in the plaque to 43.0% ± 18.6% and 45.9% ± 16.8% that of control, respectively. Histological examinations showed a significant reduction (p<0.05) of the intraplaque macrophage infiltration levels (61.9% ± 20.8% of control), number of apoptotic cells (14.5% ± 16.6%), and lipid deposition levels (53.6% ± 20.2%), as well as the plaque size (56.4% ± 11.1%). Positive correlations were observed between the 14C-FDG uptake and macrophage infiltration levels (r=0.69, p<0.001), and between the 99mTc-annexin A5 uptake level and number of apoptotic cells (r=0.69, p<0.001).
Conclusions: Remissions of inflammation and apoptosis as the potential therapeutic effects of irbesartan on atherosclerosis were identified by histological examinations and molecular imaging with 14C-FDG and99mTc-annexin A5. The accuracy and usefulness of molecular imaging for monitoring therapeutic effects are also suggested.
- © 2011 by American Heart Association, Inc.