Mechanisms of abdominal aortic aneurysm formation.

• Project/Area Number: 23591861
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SASAKI Takeshi 浜松医科大学, 技術部, 技術専門職員 (20397433)
• Co-Investigator(Kenkyū-buntansha): CHENG Xian Wu 名古屋大学, 未来社会創造機構, 准教授 (30378228) ; UNNO Naoki 浜松医科大学, 医学部, 准教授 (20291958)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腹部大動脈瘤 / 炎症細胞 / B細胞 / カテプシン / MMP / 腹部大動脈瘤(AAA) / マクロファージ / プロテアーゼ / GM-CSF / 循環器・高血圧 / アンギオテンシン / 炎症性細胞 / レニンアンギオテンシン系 / レニン-アンギオテンシン系 / マトリックスメタロプロテアーゼ（MMP) / 血管中膜・外膜

Outline of Final Research Achievements

Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals. It is suggested that inflammatory cells and proteases contribute to AAA formation. Therefore, we investigated the localization of inflammatory cells in AAA lesion. In addition, we examined the expression of proteases and their endogenous inhibitors.
Abdominal aortic tissue was harvested either from autopsy (control) or during open-repair surgery for AAA. Localization of macrophages, B cells, T cells and neutrophils were observed in AAA lesion, and significantly higher infiltration of these inflammatory cells into vascular wall of AAA was observed compared with control. More extensive immunostaining of MMPs and elastases was detected in AAA. These proteases expressed in inflammatory cells. On the other hand, expression of endogenous inhibitors against these proteases was decreased in AAA lesion.
These results suggest that inflammatory cells and some proteases may participate in AAA formation.

Research Products

• [Journal Article] Cathepsin S Activity Controls Ischemia-Induced Neovascularization in Mice (2015)
  • Author(s): Li X, Cheng XW, Hu L, Wu HX, Hao CH, Shi GP, Jiang H, Zhu E, Inoue A, Huang Z, Sasaki T, Takeshita K, Okumura K, Murohara T, Kuzuya M
  • Journal Title: International Journal of Cardiology Volume: 183 Pages: 198-208
  • DOI: 10.1016/j.ijcard.2015.01.058
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The case that the cadaver acquired a massive tattoo on the back contributed to the education for allied health professional students. (2015)
  • Author(s): T. Sasaki, J Kamei, Y Kawakami, D Kawashima, A Kawada, T Takahashi, A Takeuchi, A. Takemura, S. Kato, K. Sato.
  • Journal Title: 生物学技術研究会報告 Volume: 26
  • Acknowledgement Compliant
• [Journal Article] Decreased D2-40 immunoreactivity in stored paraffin sections and methods for preserving it. (2014)
  • Author(s): Sasaki T, Kawabata Y, Suzuki N, Tanaka H, Sano M, Kato S, Takemura A, Unno N, Kojima T, Sato K
  • Journal Title: Biotech Histochem Volume: 89 Issue: 6 Pages: 412-418
  • DOI: 10.3109/10520295.2013.821166
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lymphangiogenesis and angiogenesis in abdominal aortic aneurysm (2014)
  • Author(s): Sano M, Sasaki T, Hirakawa S, Sakabe J, Ogawa M, Baba S, Zaima N, Tanaka H, Inuzuka K, Yamamoto N, Setou M, Sato K, Konno H, Unno N
  • Journal Title: PLoS One Volume: 9 Issue: 3 Pages: e89830-e89830
  • DOI: 10.1371/journal.pone.0089830
  • Peer Reviewed / Open Access
• [Journal Article] Digesting the Atherosclerosis-like Lesion-Based Remodeled Vasculature: The Role of Cysteinyl Cathepsins in Venous Disorder. (2014)
  • Author(s): Cheng XW, Sasaki T, Kuzuya M
  • Journal Title: Thrombosis and Haemostasis Volume: in press Issue: 07 Pages: 216-218
  • DOI: 10.1160/th13-10-0889
  • Peer Reviewed / Open Access
• [Journal Article] Development of new services for technical specialist in the department of anatomy. -The recent services in anatomical education for medical students- (2014)
  • Author(s): T. Sasaki, A. Uebayashi, A. Takemura, S. Kato, K. Sato
  • Journal Title: 生物学技術研究会報告 Volume: 25 Pages: 29-32
  • Acknowledgement Compliant
• [Journal Article] Development of new services for technical specialist in the department of anatomy. The recent services in anatomical education for medical students. (2014)
  • Author(s): Sasaki T, Uebayashi A, Takemura A, Kato S, Sato K
  • Journal Title: 生物学技術研究会報告 Volume: in press
• [Journal Article] The Decrease in D2-40 Immunoreactivity of Stored Paraffin Sections and Preservation Methods to Keep the D2-40 Immunoreactivity. (2014)
  • Author(s): Sasaki T, Kawabata Y, Suzuki N, Tanaka H, Sano M, Kato S, Takemura A, Unno N, Kojima T, Sato K
  • Journal Title: Biotechnic and Histochemistry Volume: in press
  • Peer Reviewed
• [Journal Article] The case of difficult infusion of formaldehyde solution in cadavers to embalm for anatomy teaching, and an improved method for infusion. (2013)
  • Author(s): Sasaki T, Ito T, Takemura A, Kato S, Sato K
  • Journal Title: 生物学技術研究会報告 Volume: 24 Pages: 66-69
• [Journal Article] Human breast cancer tissues contain abundant phosphatidylcholine(36:1) with high stearoyl-CoA desaturase-1 expression. (2013)
  • Author(s): Ide Y, Waki M, Hayasaka T, Nishio T, Morita Y, Tanaka H, Sasaki T, Koizumi K, Matsunuma R, Hosokawa Y, Ogura H, Shiiya N, Setou M.
  • Journal Title: PLoS ONE Volume: 8 Issue: 4 Pages: e61204-e61204
  • DOI: 10.1371/journal.pone.0061204
  • Peer Reviewed
• [Journal Article] *equal contribution Adventitiavasa vasorum arteriosclerosisin abdominal aortic aneurysm (2013)
  • Author(s): Tanaka, H*., Zaima, N*., Sasaki, T., Hayasaka, T., Goto-Inoue, N., Onoue, K., Ikegami, K., Morita, Y., Yamamoto, N., Mano, Y., Sano, M., Saito, T., Sato, K., Konno, H., Setou, M
  • Journal Title: Plos One Volume: 8 Issue: 2 Pages: e57398-e57398
  • DOI: 10.1371/journal.pone.0057398
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase-2 deficiency impairs aortic atherosclerotic calcification in ApoE-deficient mice. (2013)
  • Author(s): Sasaki T, Nakamura K, Sasada K, Okada S, Cheng XW, Suzuki T, Murohara T, Sato K, Kuzuya M.
  • Journal Title: Atherosclerosis. Volume: 227(1) Issue: 1 Pages: 43-50
  • DOI: 10.1016/j.atherosclerosis.2012.12.008
  • Peer Reviewed
• [Journal Article] The Decrease in D2-40 Immunoreactivity of Stored Paraffin Sections and Preservation Methods to Keep the D2-40 Immunoreactivity. (2013)
  • Author(s): Takeshi Sasaki, Yayoi Kawabata, Naomi Suzuki, Hiroki Tanaka, Masanori Sano, Sachiho Kato, Ayana Takemura, Naoki Unno, Toshio Kojima, Kohji Sato.
  • Journal Title: Biotechnic and Histochemistry Volume: in press
  • Peer Reviewed
• [Journal Article] 系統解剖実習用の献体の防腐処置に難渋した例とその対処法 (2013)
  • Author(s): 佐々木健、伊藤武司、竹村綾奈、加藤裟智穂、佐藤康二
  • Journal Title: 生物学技術研究会報告 Volume: 24
• [Journal Article] Spine Homeostasis as a Novel Therapeutic Target for Schizophrenia. (2013)
  • Author(s): Satoru Yamagishi, Sumiko Mikawa, Hiromu Furukawa, Takeshi Sasaki, Takeshi Ito, Takatoshi Ueki and Kohji Sato.
  • Journal Title: Clinical Pharmacology & Biopharmaceutics Volume: in press
  • Peer Reviewed
• [Journal Article] Association between body weight at weaning and remodeling in the subcutaneous adipose tissue of obese adult mice with undernourishment in utero (2013)
  • Author(s): Y.K. Kohmura, N. Kanayama, K. Muramatsu, N. Tamura, C. Yaguchi, T. Uchida, K. Suzuki, K. Sugihara, S. Aoe, T. Sasaki, T. Suganami, Y. Ogawa, H. Itoh
  • Journal Title: Reprod. Sci. Volume: 20 Issue: 7 Pages: 813-827
  • DOI: 10.1177/1933719112466300
  • Peer Reviewed
• [Journal Article] CLP36 and RIL recruit α -actinin-1 to stress fibers and differentially regulate stress fiber dynamics in F2408 fibroblasts (2012)
  • Author(s): Miyazaki K, Ohno K, Tamura N, Sasaki T, Sato K
  • Journal Title: Exp Cell Res Volume: 318 Issue: 14 Pages: 1716-25
  • DOI: 10.1016/j.yexcr.2012.05.006
  • Peer Reviewed
• [Journal Article] 二種類のホルマリン色素除去法(Kardasewitsch法及びVerocay法変法)の比較検討 －免疫染色への影響－ (2012)
  • Author(s): 佐々木健*、川端弥生、鈴木直美、古田直美、谷口千津子、森田真知子、伊東宏晃、金山尚裕、小島俊男、佐藤康二
  • Journal Title: 生物学技術研究会報告 Volume: 23 Pages: 30-33
• [Journal Article] Role for cysteine protease cathepsins in heart disease: focus on biology and mechanisms with clinical implication (2012)
  • Author(s): Cheng XW, Shi GP, Kuzuya M, Sasaki T, Okumura K, Murohara T.
  • Journal Title: Circulation Volume: 125 Issue: 12 Pages: 1551-62
  • DOI: 10.1161/circulationaha.111.066712
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• [Journal Article] Osteoarthritic change is delayed in a Ctsk-knockout mouse model of osteoarthritis (2012)
  • Author(s): Kozawa E, Nishida Y, Cheng XW, Urakawa H, Arai E, Futamura N, Shi GP, Kuzuya M, Hu L, Sasaki T, Ishiguro N
  • Journal Title: Arthritis Rheum Volume: 64 Issue: 2 Pages: 454-64
  • DOI: 10.1002/art.33398
  • Peer Reviewed
• [Journal Article] Immunohistochemical detection of meconium in the fetal membrane, placenta and umbilical cord (2012)
  • Author(s): Naomi Fruta
  • Journal Title: Placenta Volume: 33 Issue: 1 Pages: 24-30
  • DOI: 10.1016/j.placenta.2011.10.007
  • Peer Reviewed
• [Journal Article] Loss of lymphatic vessels and regional lipid accumulation is associated with incompetent great saphenous vein (2011)
  • Author(s): Tanaka H, Zaima N, Sasaki T, Yamamoto N, Sano M, Konno H, Setou M, Unno N
  • Journal Title: J Vasc Surg Volume: 55 Issue: 5 Pages: 1440-8
  • DOI: 10.1016/j.jvs.2011.09.064
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• [Journal Article] Microarray analysis identifies versican and CD9 as potent prognostic markers in gastric gastrointestinal stromal tumors (2011)
  • Author(s): Setoguchi T, Konno H, et al
  • Journal Title: Cancer Science Volume: 102 Issue: 4 Pages: 883-889
  • DOI: 10.1111/j.1349-7006.2011.01872.x
  • NAID: 10029292808
  • Peer Reviewed
• [Journal Article] Inhibition of Mineralocorticoid Receptor is a Renoprotective Effect of an HMG CoA Reductase Inhibitor Pitavastatin. (2011)
  • Author(s): Cheng XW, Kuzuya M, Sasaki T, Inoue A, Hu L, Song H, Huang Z, Li P, Takeshita K, Hirashiki A, Sato K, Shi GP, Okumura K, Murohara T
  • Journal Title: Journal of Hypertension Volume: 29 Issue: 3 Pages: 542-552
  • DOI: 10.1097/hjh.0b013e328341cedf
  • Peer Reviewed
• [Journal Article] 薄切した保存標本におけるD2-40抗体を用いた免疫染色性の変化 (2011)
  • Author(s): 川端弥生、佐々木健*、鈴木直美、小島俊男
  • Journal Title: 生物学技術研究会報告 Volume: 22 Pages: 75-78
• [Journal Article] マウス粥状動脈硬化病変における脂肪染色en face解析後のパラフィン切片作成と組織学的解析 -本法による動脈硬化病変形成におけるMMP-2の関与の検討- (2011)
  • Author(s): 佐々木健*、葛谷雅文、成憲武、中村香江、鈴木直美、川端弥生、佐藤康二
  • Journal Title: 生物学技術研究会報告 Volume: 22 Pages: 71-74
• [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
  • Journal Title: Atheroslerosis Volume: 217 Issue: 2 Pages: 427-432
  • DOI: 10.1016/j.atherosclerosis.2011.03.044
  • Peer Reviewed
• [Journal Article] Angiotensin type 1 receptor blocker reduces intimal neovascularization and plaque growth in apolipoprotein E-deficient mice (2011)
  • Author(s): Cheng XW, Song H, Sasaki T, Hu L, Inoue A, Bando YK, Shi GP, Kuzuya M, Okumura K, Murohara T
  • Journal Title: Hypertension Volume: 57 Issue: 5 Pages: 981-9
  • DOI: 10.1161/hypertensionaha.110.168385
  • Peer Reviewed
• [Presentation] 背部に広範な刺青の入った解剖体が医学教育に貢献した例 ～刺青と免疫系との関連～ (2015)
  • Author(s): 佐々木健
  • Organizer: 平成26年度 浜松医科大学・技術発表会
  • Place of Presentation: 浜松
  • Year and Date: 2015-03-13
• [Presentation] 腹部大動脈瘤におけるB細胞とそのサブセットに関する研究 -IRA-B細胞について- (2015)
  • Author(s): 佐々木健、高橋巧、竹内文子、上林明日翔、竹村綾奈、加藤裟智穂、佐藤康二
  • Organizer: 第15回浜松医科学シンポジウム
  • Place of Presentation: 浜松
  • Year and Date: 2015-03-06
• [Presentation] The case that the cadaver acquired a massive tattoo on the back contributed to the education for allied health professional students. -The relationship between tattoo and human immune systems- (2015)
  • Author(s): 佐々木健、亀井淳哉、川上優、川島大喜、河田紋華、高橋巧、竹内文子、竹村綾奈，加藤裟智穂、佐藤 康二
  • Organizer: 第26回生物学技術研究会 第37回生理学技術研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2015-02-19 – 2015-02-20
• [Presentation] Mechanisms of abdominal aortic aneurysm formation. -The role of inflammatory cells- (2014)
  • Author(s): Takeshi Sasaki, Ayana Takemura, Sachiho Kato, Shunsuke Ueda, Tomoyuki Asao, Asuka Uebayashi, Hiroki Tanaka, Masanori Sano, Naoki Unno and Kohji Sato
  • Organizer: 第19回静岡健康・長寿学術フォーラム
  • Place of Presentation: 沼津
  • Year and Date: 2014-11-07 – 2014-11-08
• [Presentation] 腹部大動脈瘤の形成・進展メカニズムに関する研究－B細胞の局在と腹部大動脈瘤との関連性－ (2014)
  • Author(s): 竹村綾奈、佐々木健、加藤裟智穂、田中宏樹、佐野真規、海野直樹、上田駿介、朝生智之、上林明日翔、佐藤康二
  • Organizer: 第7回大動脈分子病態研究会
  • Place of Presentation: 久留米
  • Year and Date: 2014-08-07
• [Presentation] Development of new services for technical specialist in the department of anatomy. (2014)
  • Author(s): 佐々木健、上林明日翔、竹村綾奈、加藤裟智穂、佐藤康二
  • Organizer: 第25回生物学技術研究会 第36回生理学技術研究会
  • Place of Presentation: 自然科学研究機構 岡崎コンファレンスセンター
• [Presentation] 腹部大動脈瘤の形成・進展のメカニズムに関する研究 -炎症細胞とプロテアーゼの関与について- (2014)
  • Author(s): 佐々木健、朝生智之、上田駿介、上林明日翔、 竹村綾奈、加藤裟智穂、森田真知子、佐藤康二
  • Organizer: 第12回浜松医科学シンポジウム
  • Place of Presentation: 浜松医科大学 多目的ホール
• [Presentation] 解剖学実習における技術職員の 新しい取り組み (2014)
  • Author(s): 佐々木健
  • Organizer: 平成25年度 浜松医科大学・技術発表会
  • Place of Presentation: 浜松医科大学
• [Presentation] 腹部大動脈瘤の形成・進展メカニズムに関する組織学的研究 -B細胞の局在と腹部大動脈瘤との関連性- (2014)
  • Author(s): 竹村綾奈、加藤裟智穂、佐々木健、森田真知子、佐野真規、田中宏樹、海野直樹、佐藤康二
  • Organizer: 199回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学
• [Presentation] Mechanisms of abdominal aortic aneurysm development -The relationship among inflammatory cells, proteases, and abdominal aortic aneurysm development- (2013)
  • Author(s): Ayana Takemura, Takeshi Sasaki, Sachiho Kato, Machiko Morita, Hiroki Tanaka, Masanori Sano, Naoki Unno, Kohji Sato
  • Organizer: 第18回静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡県コンベショアーツセンター グランシップ
• [Presentation] Matrix Metalloproteinase-2 Deficiency Impairs Aortic Atherosclerotic Calcification in ApoE-Deficient Mice (2013)
  • Author(s): Sachiho Kato, Takeshi Sasaki, Ayana Takemura, Kumiko Sasada, Satoshi Okada, Kae Nakamura, Xian Wu Cheng, Toyoaki Murohara, Masafumi Kuzuya, Kohji Sato
  • Organizer: 第18回静岡健康・長寿学術フォーラム
  • Place of Presentation: 静岡県コンベショアーツセンター グランシップ
• [Presentation] 系統解剖実習用の献体の防腐処置に難渋した例とその対処法 (2013)
  • Author(s): 佐々木健、伊藤武司、竹村綾奈、加藤裟智穂、佐藤康二
  • Organizer: 第23回生物学技術研究会･第34回生理学技術研究会
  • Place of Presentation: 岡崎コンファレンスセンター
• [Presentation] 腹部大動脈瘤におけるB細胞の局在とレニン-アンギオテンシン系との関連性 (2012)
  • Author(s): 佐々木健、森田真知子、佐野真規、田中宏樹、海野直樹、佐藤康二
  • Organizer: 第72回日本解剖学会中部支部学術集会
  • Place of Presentation: じゅうろくプラザ(岐阜)
• [Presentation] 二種類のホルマリン色素除去法(Kardasewitsch法及びVerocay法変法)の比較検討 －免疫染色への影響－ (2012)
  • Author(s): 佐々木健、川端弥生、鈴木直美、古田直美、谷口千津子、金山尚裕、佐藤康二
  • Organizer: 第23回生物学技術研究会
  • Place of Presentation: 自然科学研究機構 岡崎カンファレンスセンター
• [Presentation] 二種類のホルマリン色素除去法の比較検討 －免疫染色への影響－ (2012)
  • Author(s): 川端弥生、佐々木健、鈴木直美、古田直美、谷口千津子、森田真知子、伊東宏晃、金山尚裕、佐藤康二、小島俊男
  • Organizer: 第6回浜松医科学シンポジウム
  • Place of Presentation: 浜松医科大学 多目的ホール
• [Presentation] 腹部大動脈瘤の形成・進展のメカニズムについて (2012)
  • Author(s): 佐々木健、森田真知子、佐藤康二
  • Organizer: 第6回浜松医科学シンポジウム
  • Place of Presentation: 浜松医科大学 多目的ホール
• [Presentation] 系統解剖実習用の献体の保存方法とその防腐処置に難渋した例 (2012)
  • Author(s): 佐々木健、伊藤武司、佐藤康二
  • Organizer: 平成23年度浜松医科大学・技術発表会
  • Place of Presentation: 浜松医科大学 看護棟中会議室
• [Presentation] 二種類のホルマリン色素除去法(Kardasewitsch法及びVerocay法変法)の比較検討 －免疫染色への影響－ (2012)
  • Author(s): 佐々木健、鈴木直美、川端弥生、谷口千津子、金山尚裕、佐藤康二
  • Organizer: 第117回日本解剖学会総会・全国学術集会
  • Place of Presentation: 山梨大学 甲府キャンパス
• [Presentation] ApoE欠損マウスの大動脈石灰化におけるMMP-2の関与 (2011)
  • Author(s): 佐々木健,、笹田久美子、岡田聡、中村香江、成憲武、鈴木亨、葛谷雅文 、佐藤康二
  • Organizer: 第４回大動脈瘤分子病態研究会
  • Place of Presentation: 久留米大学 筑水会館
• [Presentation] Longitudinal evaluation of subcutaneous lymphatics in secondary lymphedema model of a rat hind limb (2011)
  • Author(s): Masaki Sano, Mikako Ogawa, Takeshi Sasaki, Naoki Unno, Katsutoshi Miura, Satoshi Hirakawa, Minoru Suzuki
  • Organizer: 2011 World Molecular Imaging Congress
  • Place of Presentation: San Diego, California
• [Presentation] 免疫染色技術の再確認 -より適した固定・包埋・抗原賦活法等の選択とwebを使ったより良い抗体の選び方(探し方)-
  • Author(s): 佐々木健
  • Organizer: 平成24年度 浜松医科大学･学内技術セミナー
  • Place of Presentation: 浜松医科大学
• [Presentation] 腹部大動脈瘤の形成・進展と炎症性細胞の関連性 -特にB細胞に着目した研究-
  • Author(s): 佐々木健、竹村綾奈、加藤裟智穂、森田真知子、佐藤康二
  • Organizer: 第9回浜松医科学シンポジウム
  • Place of Presentation: 浜松医科大学
• [Presentation] 免疫染色や組織解析に使える小ワザ集 （研究会等で仕入れたものを中心に）
  • Author(s): 佐々木健
  • Organizer: 平成24年度 浜松医科大学・技術発表会
  • Place of Presentation: 浜松医科大学
• [Remarks] 浜松医科大学解剖学講座 神経機能学分野
  • URL: http://www.hama-med.ac.jp/uni_education_igakubu_igaku_shinkeikaibou.html
• [Remarks] 浜松医科大学 研究活動一覧
  • URL: http://www.hama-med.ac.jp/uni_research_kenkyu.html
• [Patent(Industrial Property Rights)] 大動脈瘤動物モデル (2011)
  • Inventor(s): 海野直樹、田中宏樹、瀬藤光利、財満信宏、佐々木健、他2名
  • Industrial Property Rights Holder: 海野直樹、田中宏樹、瀬藤光利、財満信宏、佐々木健、他2名
  • Industrial Property Number: 2011-105426
  • Filing Date: 2011