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Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of apoE(-/-) Mice: Molecular Imaging with C-14-FDG and Tc-99m-Annexin A5

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Title: Suppressive Effects of Irbesartan on Inflammation and Apoptosis in Atherosclerotic Plaques of apoE(-/-) Mice: Molecular Imaging with C-14-FDG and Tc-99m-Annexin A5
Authors: Zhao, Yan Browse this author
Watanabe, Ayahisa Browse this author
Zhao, Songji Browse this author →KAKEN DB
Kobayashi, Tatsuo Browse this author
Fukao, Keita Browse this author
Tanaka, Yoshikazu Browse this author
Nakano, Toru Browse this author
Yoshida, Tetsuya Browse this author
Takemoto, Hiroshi Browse this author
Tamaki, Nagara Browse this author →KAKEN DB
Kuge, Yuji Browse this author →KAKEN DB
Issue Date: 19-Feb-2014
Publisher: PLOS
Journal Title: Plos one
Volume: 9
Issue: 2
Start Page: e89338
Publisher DOI: 10.1371/journal.pone.0089338
PMID: 24586699
Abstract: Objectives: To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using C-14-FDG and Tc-99m-annexin A5. Background: Irbesartan has a peroxisome proliferator-activated receptor gamma (PPAR gamma) activation property in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic plaques. However, such effects of irbesartan have not been fully investigated. Molecular imaging using F-18-FDG and Tc-99m-annexin A5 is useful for evaluating inflammation and apoptosis in atherosclerotic plaques. Methods: Female apoE(-/-) mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free (control) diet for 12 weeks (n = 11/group). One week after the treatment, the mice were co-injected with C-14-FDG and Tc-99m-annexin A5, and cryostat sections of the aortic root were prepared. Histochemical examination with Movat's pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer autoradiography was carried out to evaluate the levels of C-14-FDG and Tc-99m-annexin A5 in plaques (% IDxkg). In vitro experiments were performed to investigate the mechanism underlying the effects. Results: Histological examination indicated that irbesartan treatment significantly reduced plaque size (to 56.4% +/- 11.1% of control), intra-plaque lipid deposition (53.6%+/- 20.2%) and macrophage infiltration (61.9% +/- 20.8%) levels, and the number of apoptotic cells (14.5%+/- 16.6%). C-14-FDG (43.0% +/- 18.6%) and Tc-99m-annexin A5 levels (45.9% +/- 16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-alpha stimulated THP-1 monocytes (64.8% +/- 8.4% of un-treated cells). PPAR gamma activation was observed in cells treated with irbesartan (134% +/- 36% at 3 mu M to 3329% +/- 218% at 81 mu M) by a PPAR gamma reporter assay system. Conclusions: Remissions of inflammation and apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were observed. The usefulness of molecular imaging using F-18-FDG and Tc-99m-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested.
Rights: http://creativecommons.org/licenses/by/3.0/
Type: article
URI: http://hdl.handle.net/2115/55340
Appears in Collections:アイソトープ総合センター (Central Institute of Isotope Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 久下 裕司

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