脂肪細胞由来のマイクロRNAを介した血管リモデリング制御機構の解析

2014 Fiscal Year Research-status Report

• Project/Area Number: 25461131
• Research Institution: The University of Tokushima
• Principal Investigator: 八木 秀介 徳島大学, ヘルスバイオサイエンス研究部, 助教 (00507650)
• Co-Investigator(Kenkyū-buntansha): 石田 昌義 琉球大学, 医学(系)研究科(研究院), 助教 (50643251) [Withdrawn] ; 佐田 政隆 徳島大学, ヘルスバイオサイエンス研究部, 教授 (80345214)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: マイクロRNA

Outline of Annual Research Achievements

血管周囲の脂肪細胞から分泌されるmiR-100が血管平滑筋に作用し血管炎症や細胞増殖を制御する可能性がある。

我々は、miR-100が脂肪細胞や血清に存在することを見出し、このmiR-100は、血管内皮細胞や平滑筋細胞増殖に重要な分子であるmTORを標的とすることを明らかにした。

またmiR-100がそれぞれの細胞においてどのように機能しているかは不明であった。我々は、脂肪細胞培養液中のmiR100を血管平滑筋細胞に投与し、脂肪細胞から分泌されたmiR-100が、血管平滑筋細胞に進入し、血管平滑筋内のmiR100の濃度を上昇させ、mTORの発現抑制を介して、血管平滑筋の細胞数の変化、または増殖アッセイにて細胞増殖を抑制することを確認しつつある。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

マイクロRNA量の評価に必須であるqPCRは既に確立している方法であり研究はおおむね順調に進行していると思われる。

Strategy for Future Research Activity

脂肪から分泌されたmiR100が血管平滑筋増殖を抑制するかどうか動物実験にて検証していく。また臨床検体からもmiR100の平滑筋抑制作用を検討する。

Research Products

• [Journal Article] Effects of docosahexaenoic acid on the endothelial function in patients with coronary artery disease. (2015)
  • Author(s): Yagi S, Aihara K, Fukuda D, Takashima A, Hara T, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: J Atheroscler Thromb. Volume: 22 Pages: 447-454
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Plasma MicroRNA-100 Is Associated With Coronary Plaque Vulnerability. (2015)
  • Author(s): Soeki T, Yamaguchi K, Niki T, Uematsu E, Bando S, Matsuura T, Ise T, Kenya K, Hotchi J, Tobiume T, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Shimabukuro M, Sata M.
  • Journal Title: Circ J. Volume: 79 Pages: 413-418.
  • DOI: 10.1253/circj.CJ-14-0958.
  • Peer Reviewed / Open Access
• [Journal Article] Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease. (2015)
  • Author(s): Kimura S, Ueda Y, Ise T, Yagi S, Iwase T, Nishikawa K, Yamaguchi K, Yamada H, Soeki T, Wakatsuki T, Katoh S, Akaike M, Yasui N, Sata M. Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.
  • Journal Title: Int Heart J. Volume: 56 Pages: 105-109.
  • DOI: 10.1161/CIRCULATIONAHA.113.001533.
  • Peer Reviewed
• [Journal Article] Rivaroxaban, a novel oral anticoagulant, attenuates atherosclerotic plaque progression and destabilization in ApoE-deficient mice. (2015)
  • Author(s): Hara T, Fukuda D, Tanaka K, Higashikuni Y, Hirata Y, Yagi S, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Sata M.
  • Journal Title: Atherosclerosis. Volume: 印刷中 Pages: 印刷中
  • DOI: 10.1016/j.atherosclerosis.2015.03.023.
  • Peer Reviewed
• [Journal Article] Serial Imaging Changes During Treatment of IgG4-related Disease with Multiple Pseudo Tumors. (2015)
  • Author(s): Kusunose K, Hotchi J, Takagawa Y, Nishio S, Ise T, Tobiume T, Yamaguchi K, Yagi S, Iwase T, Yamada H, Soeki T, Wakatsuki T, Sata M.
  • Journal Title: Circulation Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed
• [Journal Article] Impact of indoxyl sulfate, a uremic toxin, on non-culprit coronary plaque composition assessed by integrated backscatter intravascular ultrasound. (2015)
  • Author(s): Yamazaki H, Yamaguchi K, Soeki T, Wakatsuki T, Niki T, Taketani Y, Kitaoka A, Kusunose K, Ise T, Tobiume T, Yagi S, Iwase T, Yamada H, Sata M.
  • Journal Title: Circ J. Volume: 印刷中 Pages: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Association of lower limb muscle mass and energy expenditure with visceral fat mass in healthy men. (2014)
  • Author(s): Yagi S, Kadota M, Aihara K, Nishikawa K, Hara T, Ise T, Ueda Y, Iwase T, Akaike M. Shimabukuro M, Katoh S, Sata M.
  • Journal Title: Diabetol Metab Syndr. Volume: 6 Pages: 1-5
  • DOI: doi: 10.1186/1758-5996-6-27.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Acute pulmonary thromboembolism from deep vein thrombosis induced by trauma to the popliteal vein with a tennis racket (2014)
  • Author(s): Ise T, Iwase T, Masuda S, Yagi S, Akaike M, Nishio S, Niki T, Yamaguchi K, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Sata M.
  • Journal Title: Journal of Cardiology Cases Volume: 9 Pages: 162-164
  • DOI: doi:10.1016/j.jccase.2014.01.001
  • Peer Reviewed / Open Access
• [Journal Article] Pre-load stress echocardiography for predicting the prognosis in mild heart failure. (2014)
  • Author(s): Yamada H, Kusunose K, Nishio S, Bando M, Hotchi J, Hayashi S, Ise T, Yagi S, Yamaguchi K, Iwase T, Soeki T, Wakatsuki T, Sata M.
  • Journal Title: JACC Cardiovasc Imaging Volume: 7 Pages: 641-649
  • DOI: 10.1016/j.jcmg.2014.04.009.
  • Peer Reviewed
• [Journal Article] High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients. (2014)
  • Author(s): Yagi S, Aihara K, Kondo T, Endo I, Hotchi J, Ise T, Iwase T, Akaike M, Matsumoto T, Sata M.
  • Journal Title: Endocr J. Volume: 61 Pages: 727-733.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Pentraxin 3 is a local inflammatory marker in atrial fibrillation. (2014)
  • Author(s): Soeki T, Bando S, Uematsu E, Matsuura T, Niki T, Ise T, Kusunose K, Hotchi J, Ueda Y, Tomita N, Yamaguchi K, Yagi S, Fukuda D, Taketani Y, Iwase T, Yamada H, Wakatsuki T, Shimabukuro M, Sata M.
  • Journal Title: Heart Vessels Volume: 29 Pages: 653-658.
  • DOI: 10.1007/s00380-013-0400-8.
  • Peer Reviewed
• [Journal Article] Cardiac Rehabilitation Reduces Serum Levels of Oxidized Low-Density Lipoprotein. (2014)
  • Author(s): Takashima A, Ise T, Yagi S, Iwase T, Kimura S, Ueda Y, Nishikawa K, Ishii A, Niki T, Yamaguchi K, Taketani Y, Yamada H, Soeki T, Wakatsuki T, Katoh S, Akaike M, Sata M.
  • Journal Title: Circ J. Volume: 78 Pages: 2682-2687.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNA-378 regulates adiponectin expression in adipose tissue: A new plausible mechanism. (2014)
  • Author(s): Ishida M, Shimabukuro M, Yagi S, Nishimoto S, Kozuka C, Fukuda D, Soeki T, Masuzaki H, Tsutsui M, Sata M.
  • Journal Title: PLoS One Volume: 9 Pages: e111537
  • DOI: 10.1371/journal.pone.0111537.
  • Peer Reviewed / Open Access
• [Journal Article] Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease. (2014)
  • Author(s): Yagi S, Hara T, Ueno R, Aihara K, Fukuda D, Takashima A, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: Nutr J. Volume: 13 Pages: 1-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Increase in serum triglyceride was associated with coronary plaque vulnerability in a patient with rheumatoid arthritis. (2014)
  • Author(s): Yagi S, Fujimura M, Akaike M, Aihara K, Iwase T, Tada M, Sumitomo-Ueda Y, Ise T, Yamaguchi K, Wakatsuki T, Matsumoto T, Sata M.
  • Journal Title: Journal of Cardiology Cases Volume: 10 Pages: 54-57
  • DOI: doi:10.1016/j.jccase.2014.04.009
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension. (2014)
  • Author(s): Yagi S, Takashima A, Mitsugi M, Wada T, Hotchi J, Aihara K, Hara T, Ishida M, Fukuda D, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: Ther Clin Risk Manag. Volume: 11 Pages: 83-88
  • DOI: 10.2147/TCRM.S72299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Post-transcriptional regulation of adiponectin by microRNA-378 in adipose tissue: a novel mechanism for hypoadiponectinemia. (2014)
  • Author(s): Shimabukuro M, Ishida M, Yagi S, Fukuda D, Soeki T, Sata M.
  • Organizer: ESC Congress 2014
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2014-06-20 – 2014-06-24