S-EPMC3929710 - Suppressive effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques of apoE-/- mice: molecular imaging with 14C-FDG and 99mTc-annexin A5. - OmicsDI

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Dataset Information

Suppressive effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques of apoE-/- mice: molecular imaging with 14C-FDG and 99mTc-annexin A5.

ABSTRACT:

Objectives

To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using (14)C-FDG and (99m)Tc-annexin A5.

Background

Irbesartan has a peroxisome proliferator-activated receptor gamma (PPAR?) 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 (18)F-FDG and (99m)Tc-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 (14)C-FDG and (99m)Tc-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 (14)C-FDG and (99m)Tc-annexin A5 in plaques (%ID×kg). 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%). (14)C-FDG (43.0%±18.6%) and (99m)Tc-annexin A5 levels (45.9%±16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-? stimulated THP-1 monocytes (64.8%±8.4% of un-treated cells). PPAR? activation was observed in cells treated with irbesartan (134%±36% at 3 µM to 3329%±218% at 81 µM) by a PPAR? 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 (18)F-FDG and (99m)Tc-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC3929710 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Suppressive effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques of apoE-/- mice: molecular imaging with 14C-FDG and 99mTc-annexin A5.

Zhao Yan Y Watanabe Ayahisa A Zhao Songji S Kobayashi Tatsuo T Fukao Keita K Tanaka Yoshikazu Y Nakano Toru T Yoshida Tetsuya T Takemoto Hiroshi H Tamaki Nagara N Kuge Yuji Y

PloS one 20140219 2

<h4>Objectives</h4>To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using (14)C-FDG and (99m)Tc-annexin A5.<h4>Background</h4>Irbesartan has a peroxisome proliferator-activated receptor gamma (PPARγ) 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, su ...[more]

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