The mechanism of atherosclerotic plaque disruption in experimental animal model. The concept of the involvement of cathepsins.
| Project/Area Number |
21700447
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
SASAKI Takeshi Hamamatsu University School of Medicine, 技術部, 技術専門職員 (20397433)
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| Research Collaborator |
KUZUYA Masafumi 名古屋大学, 大学院・医学系研究科, 教授 (10283441)
CHENG Xian Wu 名古屋大学, 医学部, 講師 (30378228)
NAKAMURA Kae ミシガン大学, Cardiovasc center, 研究員
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | プラーク破綻 / カテプシン / アンギオテンシン1型受容体 / 細胞外マトリックス / マクロファージ / 動脈硬化症 / 実験動物モデル / imaging mass spectrometry / 炎症細胞 |
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| Research Abstract |
Although it has been suggested that the renin-angiotensin (RA) system and cathepsins contribute to the development and vulnerability of atherosclerotic plaque, the interaction of the RA system and cathepsins is unclear. Thus, we investigated the effects of an angiotensin II type 1 receptor (AT1) antagonist, olmesartan, on the levels of cathepsins in brachiocephalic atherosclerotic plaque and plaque stabilization in apolipoprotein E (apoE)-deficient mice receiving a high-fat diet. Under a high fat diet, treatment with olmesartan (3 mg/kg per day) maintained collagen and elastin at high levels and attenuated the plaque development and cathepsin S (Cat S) level in the atherosclerotic plaque of apoE-deficient mice. The administration of olmesartan suppressed the accumulation of macrophages in plaque. Immunoreactivities of Cat S and AT1 were observed in macrophages. The amount of Cat S mRNA and the macrophage-mediated collagenolytic and elastolytic activities in cultured macrophages were increased by exposure to angiotensin II (Ang II), and these effects were diminished by olmesartan and the NADPH-oxidase inhibitor apocynin. These results suggested that Cat S derived from macrophages is involved in the mechanisms of atherosclerotic plaque vulnerability, and AT1 blocker maintained the plaque stabilization alongside the suppression of Cat S and macrophage activities.
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Report
(3 results)
Research Products
(59 results)
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[Journal Article] Imaging mass spectrometry-based histopathologic examination of atherosclerotic lesions.2011
Author(s)
Nobuhiro Zaima, Takeshi Sasaki, Hiroki Tanaka, Xian Wu Cheng, Kenji Onoue, Takahiro Hayasaka, Naoko Goto-Inoue, Hirofumi Enomoto, Naoki Unno, Masafumi Kuzuya, Mitsutoshi Setou
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Related Report
Peer Reviewed
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[Journal Article] Microarray Analysis Identifies Versican and CD9 as Potent Prognostic Markers in Gastric Gastrointestinal Stromal Tumors.2011
Author(s)
Tomohiko Setoguchi, Hirotoshi Kikuchi, Masayoshi Yamamoto, Megumi Baba, Manabu Ohta, Kinji Kamiya, Tatsuo Tanaka, Satoshi Baba, Naoko Goto-Inoue, Mitsutoshi Setou, Takeshi Sasaki, Hiroki Mori, Haruhiko Sugimura, Hiroyuki Konno.
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Journal Title
Cancer Science 102(4)
Pages: 883-889
NAID
Related Report
Peer Reviewed
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[Journal Article] Inhibition of Mineralocorticoid Receptor is a Renoprotective Effect of an HMG CoA Reductase Inhibitor Pitavastatin.2011
Author(s)
Xian Wu Cheng, Masafumi Kuzuya, Takeshi Sasaki, Aiko Inoue, Lina Hu, Haizhen Song, Zhe Huang, Ping Li, Kyosuke Takeshita, Akihiro Hirashiki, Kohji Sato, Guo-Ping Shi, Kenji Okumura, Toyoaki Murohara
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Journal Title
Journal of Hypertension 29(3)
Pages: 542-552
Related Report
Peer Reviewed
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[Journal Article] AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice.2010
Author(s)
Takeshi Sasaki, Masafumi Kuzuya, Kae Nakamura, Xian Wu Cheng, Taiju Hayashi, Haizhen Song, Lina Hu, Kenji Okumura, Toyoaki Murohara, Akihisa Iguchi, Kohji Sato
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Journal Title
Atherosclerosis 210(2)
Pages: 30-437
Related Report
Peer Reviewed
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[Journal Article] Imaging Mass Spectrometry Reveals Unique Lipid Distribution in Primary Varicose Veins.2010
Author(s)
Hiroki Tanaka, Nobuhiro Zaima, Naoto Yamamoto, Daisuke Sagara, Minoru Suzuki, Motohiro Nishiyama, Yuuki Mano, Masanori Sano, Takahiro Hayasaka, Naoko Goto-Inoue, Takeshi Sasaki, Hiroyuki Konno, Naoki Unno, Mitsutoshi Setou.
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Journal Title
European Journal of Vascular and Endovascular Surgery 40(5)
Pages: 657-663
Related Report
Peer Reviewed
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[Journal Article] Exercise Training Stimulates Ischemia-induced Neovascularization via PI3K/Akt-dependent HIF-1α Reactivation in Mice of Advanced Age.2010
Author(s)
Xian Wu Cheng, Masafumi Kuzuya, Weon Kim, Haizhen Song, Lina Hu, Aiko Inoue, Qun Di, Kae Nakamura, Takeshi Sasaki, Guo-Ping Shi, Kenji Okumura, Toyoaki Murohara.
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Journal Title
Circulation 122(7)
Pages: 707-716
Related Report
Peer Reviewed
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[Journal Article] Ca^<2+> channel blocker benedipine promotes coronary angiogenesis and reduces both left ventricular diastolic stiffness and mortality in hypertensive rats.2010
Author(s)
Takeo Nishizawa, Xian Wu Cheng, Koji Obata, Kazuo Nagata, Takashi Yamada, Hideo Izawa, Takeshi Sasaki, Akihiro Hirashiki, Akiko Noda, Kyosuke Takeshita, Guo-Ping Shi, Masafumi Kuzuya, Kenji Okumura, Toyoaki Murohara.
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Journal Title
Journal of Hypertension 28(7)
Pages: 1515-1526
Related Report
Peer Reviewed
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[Journal Article] AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice.2010
Author(s)
Sasaki T, Kuzuya M, Nakamura K, Cheng XW, Hayashi T, Song H, Hu L, Okumura K, Murohara T, Iguchi A, Sato K
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Journal Title
Atherosclerosis (accepted)
Related Report
Peer Reviewed
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[Journal Article] Ca2+ channel blocker benidipine promotes coronary angiogenesis and reduces both left-ventricular diastolic stiffness and mortality in hypertensive rats2010
Author(s)
Nishizawa T, Cheng XW, Jin Z, Obata K, Nagata K, Hirashiki A, Sasaki T, Noda A, Takeshita K, Izawa H, Shi G-P, Kuzuya M, Okumura K, Murohara T
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Journal Title
Journal of Hypertension (accepted)
Related Report
Peer Reviewed
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[Presentation] Exercise Training Stimulates Neovascularization in Response to Ischemia via HIF-1α-VEGF- mediated Activation of MMP-2 in Advanced Age.2009
Author(s)
Xian Wu Cheng, Masafumi Kuzuya, Lina Hu, Haizhen Song, Aiko Inoue, Kae Nakamura, Takeshi Sasaki, Kenji Okumura, Toyoaki Murohara
Organizer
American Heart Association, Scientific Sections 2009.
Place of Presentation
Florida, USA
Related Report
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[Presentation] AT1 Blockade Attenuates Atherosclerotic Plaque Destabilization Thorough the Suppression of Cathepsin S Activity in ApoE-Deficient Mice.2009
Author(s)
Takeshi Sasaki, Masafumi Kuzuya, Kae Nakamura, Xian Wu Cheng, Taiju Hayashi, Yoko Masuda, Kenji Okumura, Toyoaki Murohara, Akihisa Iguchi, Kohji Sato
Organizer
The 9th Kyungpoo-Hamamastu Joint Medical Symposium
Place of Presentation
Taegu, Korea
Related Report
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