The role of SMP30 in formation and progression of abdominal aortic aneurysm and atherosclerosis.

• Project/Area Number: 16K09476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: Suzuki Satoshi 福島県立医科大学, 医学部, 助教 (60536944)
• Research Collaborator: Sato Akihiko ; Watanabe Syunsuke
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: SMP30 / 腹部大動脈瘤 / inflammation / Apolipoprotein E / 動脈硬化 / 動脈瘤 / 加齢 / ApoE

Outline of Final Research Achievements

We administered angiotensin II (AngII) to wild type (WT) mice, SMP30 knockout (SMP30-KO) mice, apolipoprotein E knockout (ApoE-KO) mice, and SMP30/ApoE double knockout (DKO) mice to evaluate the SMP30 in the development of abdominal aortic aneurysm. Maximum diameter of abdominal aorta after AngII administration was largest in DKO mice followed by ApoE-KO mice, however abdominal aorta was not dilated in SMP30-KO mice. Inflammatory markers in aortic tissue increased in DKO mice followed by ApoE-KO mice, however these markers was not expressed in SMP30-KO mice. From these results, we demonstrated that SMP30 would suppress the formatioin of abdominal aortic aneurysm via suppresion of inflammatory marker expression.

Academic Significance and Societal Importance of the Research Achievements

SMP30が炎症反応の抑制作用を介して大動脈瘤の形成を抑制することが明らかになった。ただし、AngIIの非存在下ではこれらの作用は見られなかったことからSMP30のこのような作用の詳細は未だ明らかではない。
本研究よりSMP30が大動脈瘤の形成および治療の標的になり得ることが示唆された。今後益々、高齢化と食生活の欧米化により動脈硬化性疾患の増加が予想されるわが国においては、大動脈瘤の治療あるいは進行を遅らせる薬の開発は切実である。そういった意味においても大動脈瘤の形成を抑制する可能性があるSMP30の効果が示された本研究の意義は大きいと考える。

Research Products

• [Journal Article] Prognostic significance of periodic leg movements during sleep in heart failure patients. (2016)
  • Author(s): Yoshihisa A, Suzuki S, Kanno Y, Takiguchi M, Sato A, Miura S, Masuda A, Yokokawa T, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Sato T, Oikawa M, Saitoh S, Takeishi Y.
  • Journal Title: Int J Cardiol Volume: 212 Pages: 11-13
  • DOI: 10.1016/j.ijcard.2016.03.007
  • Peer Reviewed
• [Journal Article] Plasma Levels of Receptor for Advanced Glycation End-Products and High-Mobility Group Box 1 in Patients With Pulmonary Hypertension (2016)
  • Author(s): Satoshi Suzuki, Kazuhiko Nakazato, Koichi Sugimoto, Akiomi Yoshihisa, Takayoshi Yamaki, Hiroyuki Kunii, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
  • Journal Title: International Heart Journal Volume: 57 Issue: 2 Pages: 234-240
  • DOI: 10.1536/ihj.15-188
  • NAID: 130005139753
  • ISSN: 1349-2365, 1349-3299
  • Peer Reviewed / Open Access
• [Journal Article] Association between levels of anti-angiogenic isoform of vascular endothelial growth factor A and pulmonary hypertension (2016)
  • Author(s): Satoshi Suzuki, Akiomi Yoshihisa, Tetsuro Yokokawa, Tomofumi Misaka, Nobuo Sakamoto, Koichi Sugimoto, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Yasuchika Takeishi
  • Journal Title: International Journal of Cardiology Volume: 222 Pages: 416-420
  • DOI: 10.1016/j.ijcard.2016.07.277
  • Peer Reviewed
• [Journal Article] Prognostic Significance of Insomnia in Heart Failure (2016)
  • Author(s): Yuki Kanno, Akiomi Yoshihisa, Shunsuke Watanabe, Mai Takiguchi, Tetsuro Yokokawa, Akihiko Sato, Shunsuke Miura, Takeshi Shimizu, Yuichi Nakamura, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Shu-ichi Saitoh, Yasuchika Takeishi
  • Journal Title: Circulation Journal Volume: 80 Issue: 7 Pages: 1571-1577
  • DOI: 10.1253/circj.CJ-16-0205
  • NAID: 130005158908
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] The CHA2DS2-VASc score as a predictor of high mortality in hospitalized heart failure patients (2016)
  • Author(s): Akiomi Yoshihisa, Shunsuke Watanabe, Yuki Kanno, Mai Takiguchi, Akihiko Sato, Tetsuro Yokokawa, Shunsuke Miura, Takeshi Shimizu, Satoshi Abe, Yasuchika Takeshi, et al
  • Journal Title: ESC Heart Failure Volume: 3 Issue: 4 Pages: 261-269
  • DOI: 10.1002/ehf2.12098
  • Peer Reviewed / Open Access
• [Presentation] The DPP4 inhibition ameliorates cardiac function by inhibiting the cleavage of HMGB-1 in diabetic mice after myocardial infarction (2016)
  • Author(s): Akihiko Sato, Satoshi Suzuki, Shunsuke Watanabe, Takeshi Shimizu, Yuichi Nakamura, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi.
  • Organizer: The 33rd Annual Meeting of the International Society for Heart Research (ISHR) Japanese Section
  • Place of Presentation: Tokyo
  • Year and Date: 2016-12-16
  • Int'l Joint Research
• [Presentation] Association between sleep disordered breathing and arterial stiffness in heart failure patients with reduced or preserved ejection fraction (2016)
  • Author(s): Satoshi Suzuki, Akiomi Yoshihisa, Yu Sato, Tetsuro Yokokawa, Shunsuke Miura, Takamasa Sato, Shunsuke Watanabe, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Yasuchika Takeishi.
  • Organizer: Scientific Sessions of American Heart Association 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Associations between acylcarnitine to total carnitine ratio and adverse prognosis in heart failure patients with reduced or preserved ejection fraction. (2016)
  • Author(s): Shunsuke Watanabe, Akiomi Yoshihisa, Yu Sato, Tetsuro Yokokawa, Shunsuke Miura, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Yasuchika Takeishi.
  • Organizer: Scientific Sessions of American Heart Association 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Liver fibrosis score predicts mortality in heart failure patients with preserved ejection fraction. (2016)
  • Author(s): Yu Sato, Akiomi Yoshihisa, Shunsuke Watanabe, Tetsuro Yokokawa, Shunsuke Miura, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Shu-ichi Saitoh, Yasuchika Takeishi.
  • Organizer: Scientific Sessions of American Heart Association 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Pulmonary hypertension with altered eNOS and ALK-1 signaling in the autoimmuno-disease mice. (2016)
  • Author(s): Koichi Sugimoto, Akihiko Sato, Shunsuke Watanabe, Satoshi Suzuki, Takeshi Machida, Shu-ichi Saitoh, Hideharu Sekine, Yasuchika Takeishi.
  • Organizer: Scientific Sessions of American Heart Association 2016
  • Place of Presentation: New Orleans
  • Year and Date: 2016-11-12
  • Int'l Joint Research