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Beneficial effect of anti-platelet therapies on atherosclerotic lesion formation assessed by phase-contrast X-ray CT imaging

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Abstract

We have applied an imaging system of phase-contrast X-ray CT to the detection of atherosclerotic plaque components by means of the differences of tissue mass densities. In this study, we investigated the effect of the anti-platelet therapies, widely used for secondly prevention of cardiovascular events, on plaque stability and examined whether this novel technique could detect the changes of plaque components under the therapy. Apolipoprotein E-deficient mice were fed on high-cholesterol diet alone and either with 0.1% cilostazol or clopidogrel for 10 weeks. We assessed atherosclerotic lesion volumes and components at brachiocephalic artery by the phase-contrast X-ray CT imaging and histochemistry. The phase-contrast X-ray CT imaging could reveal that cilostazol and clopidogrel significantly decreased atherosclerotic lesion volumes at brachiocephalic artery (31.2% reduction in cilostazol group and 37.4% reduction in clopidogrel group), compared with control group. In addition, the mass densities calculated by this method revealed the anti-platelet treatment increased stable plaque areas including high collagen content, but decreased unstable plaque areas including lipid and macrophage content. These findings were confirmed by histological analyses. Real-time PCR analyses indicated that anti-platelets inhibited gene expressions of cytokines and adhesion molecules, such as IFNγ and ICAM-1. Anti-platelet therapies had a beneficial effect on plaque stability maybe due to anti-inflammatory actions. Phase-contrast X-ray CT imaging could quantify the plaque volume and qualify the plaque components affected by anti-platelet therapies. This novel phase-contrast X-ray CT imaging system could be a plausible method to detect the unstable plaque non-invasively in the future.

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Acknowledgments

This work was supported by Grant-in-aid for Scientific Research Japan Society for the Promotion of Science, and was carried out under the approval of the committee of SPring-8, Japan as the Medical-Biology Trial Use (Proposal No. 2008A1872).

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Masafumi Takeda, Tomoya Yamashita, Masakazu Shinohara, Naoto Sasaki, Hideto Tawa, Kenji Nakajima & Ken-ichi Hirata

  2. Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

    Atsushi Momose

Authors
  1. Masafumi Takeda
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  2. Tomoya Yamashita
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  3. Masakazu Shinohara
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  4. Naoto Sasaki
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  5. Hideto Tawa
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  6. Kenji Nakajima
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  7. Atsushi Momose
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  8. Ken-ichi Hirata
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Correspondence to Tomoya Yamashita.

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Takeda, M., Yamashita, T., Shinohara, M. et al. Beneficial effect of anti-platelet therapies on atherosclerotic lesion formation assessed by phase-contrast X-ray CT imaging. Int J Cardiovasc Imaging 28, 1181–1191 (2012). https://doi.org/10.1007/s10554-011-9910-6

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  • DOI: https://doi.org/10.1007/s10554-011-9910-6

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