Abstract 10107: Irbesartan Reduces Atherosclerosis in Watanabe Heritable Hyperlipidemic (WHHL) Rabbits: Non-invasive Imaging of Inflammation With 18F-FDG PET
Background: We previously reported that irbesartan, an ARB with a PPARγ activation property, can suppress the progression of atherosclerosis through anti-inflammation effects. Non-invasive imaging of key factors such as inflammation involved in the therapeutic effects should be useful for monitoring the therapeutic effects.
Object: To assess the usefulness of inflammation imaging with 18F-FDG PET in evaluating the anti-atherogenetic effects of irbesartan.
Methods: Male WHHL rabbits were given a diet containing irbesartan (75 mg/kg/day) for 9 months. After 2-week discontinuation of the treatment, rabbits (n=14) underwent 18F-FDG PET for 3 hours. 18F-FDG uptake in the lesion (thoracic aorta) was determined, and calculated as a ratio with respect to that in the liver. Serial cryostat sections of the lesion were produced for autoradiography and histological examinations. The 18F-FDG uptake (%IDxkg) was also evaluated in the autoradiograms. Movat’s pentachrome (plaque size), RAM-11 (macrophage infiltration), and Oil Red O (lipid deposition) staining were performed. Similar experiments were performed with age-matched rabbits on irbesartan free diet (n=14) as a control.
Results: In the thoracic lesions of control rabbits, diffuse intimal thickening with intensive macrophage infiltration and lipid deposition were observed. Irbesartan treatment significantly reduced (p<0.05) the plaque size (43.1% of control), intra-plaque macrophage infiltration (48.1%) and lipid deposition (35.6%). PET imaging clearly visualized the thoracic lesions of control rabbits, and showed a significant reduction in 18F-FDG uptake in the lesions of irbesartan-treated rabbits (78.8% of control). Autoradiographic studies confirmed that 18F-FDG uptake in plaques were positively correlated with the plaque size (r=0.65, p<0.05) and macrophage infiltration level (r=0.57, p<0.05).
Conclusion: Irbesartan treatment significantly reduced inflammation in the atherosclerotic lesions of hyperlipidemic rabbits, and consequently decreased the 18F-FDG uptake levels in the lesion. Non-invasive imaging with 18F-FDG PET is useful for evaluating the therapeutic effects of ARBs, reflecting inflammation, a key-factor involved in the therapeutic effects.
- © 2013 by American Heart Association, Inc.