血管新生因子に対するインクレチン関連薬の効果

2015 Fiscal Year Research-status Report

• Project/Area Number: 15K19390
• Research Institution: Fukushima Medical University
• Principal Investigator: 中村 裕一 福島県立医科大学, 医学部, その他 (10745798)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: インクレチン / DPP4 / HMGB1 / 心筋梗塞 / 血管新生 / 増殖因子

Outline of Annual Research Achievements

HMGB1心筋特異的過剰発現(TG)マウスと野生型(WT)マウスにそれぞれstreptozocin (STZ)を投与し、糖尿病モデル(DM)マウスを作成した。いずれも血中のDPP4活性は上昇していた。STZ投与3週間後にマウスの冠動脈を結紮し心筋梗塞を作成した。梗塞巣の大きさ、心エコーでの心機能、血中HMGB1濃度、梗塞境界域での血管新生をWTマウス、TGマウス、WT-DMマウス、TG-DMマウスで比較検討した。
引き続きSTZ投与後、血糖とDPP4活性が上昇していることを確認後にDPP4阻害薬(DPP4i) anagliptinを経口投与を開始し、STZ投与3週間後に、それぞれWT-DM-DPP4iマウス、TG-DM-DPP4iマウスに心筋梗塞を作成し、梗塞巣の大きさ、心エコーでの心機能、血中HMGB1濃度、梗塞境界域での血管新生について6群間で比較検討した。

Current Status of Research Progress

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

Reason

当初の予定通り、DMモデルマウスを作成し心筋梗塞を作成できた。また、DPP4阻害薬投与によりHMGB1とDPP4の関連が明らかにすることができた。
今後は、タンパクの測定などを行う予定である。

Strategy for Future Research Activity

今後は、タンパクの測定などを行う予定である。
また、GLP-1受容体作動薬など他のインクレチン製剤とDPP4阻害薬の比較を行う。

Research Products

• [Journal Article] The association between circulating anti-angiogenic isoform of vascular endothelial growth factor and clinical profiles in patients with peripheral artery disease (2016)
  • Author(s): Sato A, Yoshihisa A, Yokokawa T, Shimizu T, Nakamura Y, Misaka T, Kamioka M, Kaneshiro T, Suzuki S, Kunii H, Saitoh S, Takeishi Y
  • Journal Title: Int J Cardiol Volume: 207 Pages: 368-369
  • DOI: 10.1016/j.ijcard.2016.01.189
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] High Mobility Group Box 1 Promotes Angiogenesis from Bone Marrow-derived Endothelial Progenitor Cells after Myocardial Infarction (2015)
  • Author(s): Yuichi Nakamura, Satoshi Suzuki, Takeshi Shimizu, Makiko Miyata, Tetsuro Shishido, Kazuhiko Ikeda, Shu-ichi Saitoh, Isao Kubota, Yasuchika Takeishi
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 22 Pages: 570-581
  • DOI: 10.5551/jat.27235
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Impact of peripheral artery disease on prognosis in hospitalized heart failure patients (2015)
  • Author(s): Yuichi Nakamura, Akiomi Yoshihisa, Mai Takiguchi, Takeshi Shimizu, Hiroyuki Yamauchi, Shoji Iwaya, Takashi Owada, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, and Yasuchika Takeishi
  • Journal Title: Circulation Journal Volume: 79 Pages: 785–793
  • DOI: 10.1253/circj.CJ-14-1280
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Association of hypocalcemia with mortality in hospitalized patients with heart failure and chronic kidney disease (2015)
  • Author(s): Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Iwaya S, Owada T, Miyata M, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: J Card Fail Volume: 21 Pages: 621-627
  • DOI: 10.1016/j.cardfail.2015.04.015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Relationship of hyperuricemia with mortality in heart failure patients with preserved ejection fraction (2015)
  • Author(s): Shimizu T, Yoshihisa A, Kanno Y, Takiguchi M, Sato A, Miura S, Nakamura Y, Yamauchi H, Owada T, Abe S, Sato T, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 309 Pages: H1123-H1129
  • DOI: 10.1152/ajpheart .00533.2015
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cardio-protective effects of pentraxin 3 produced from bone marrow-derived cells against ischemia/reperfusion injury (2015)
  • Author(s): Shimizu T, Suzuki S, Sato A, Nakamura Y, Ikeda K, Saitoh S, Misaka S, Shishido T, Kubota I, Takeishi Y
  • Journal Title: J Mol Cell Cardiol Volume: 89 Pages: 306-313
  • DOI: 10.1016/j.yjmcc.2015.10.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Beneficial impact of dipeptidyl-peptidase-4 inhibitors on mortality of hospitalized heart failure patients with diabetes mellitus. (2016)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] Hyperuricemia is a prognostic predictor of all-cause mortality in heart failure with preserved ejection fraction. (2016)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Sato A, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] Impact of n-3 polyunsaturated fatty acids on mortality of patients with hospitalized heart failure patients. (2016)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] Prognostic impact of periodic leg movements in hospitalized heart failure patients. (2016)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] The association between plasma level of antiangiogenic isoform of vascular endothelial growth factor and clinical profile of peripheral artery disease. (2016)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] The CHA2DS2-VASc score predicts high mortality in hospitalized heart failure patients. (2016)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-20 – 2016-03-22
• [Presentation] Associations of insomnia with prognosis in hospitalized heart failure patients. (2016)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2016-03-18 – 2016-03-20
• [Presentation] eneficial impact of dipeptidyl-peptidase-4 inhibitors on mortality of patients with hospitalized heart failure patients with diabetes mellitus. (2015)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Cardio-protective effects of pentraxin 3 produced from bone marrow-derived cells against ischemia/reperfusion injury. (2015)
  • Author(s): Shimizu T, Suzuki S, Sato A, Nakamura Y, Saitoh S, Mantovani A, Shishido T, Kubota I, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Impact of n-3 polyunsaturated fatty acids on mortality of patients with hospitalized heart failure patients. (2015)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Impact of serum uric acid on mortality in heart failure with preserved ejection fraction. (2015)
  • Author(s): himizu T, Yoshihisa A, Takiguchi M, Miura S, Sato A, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Prognostic impact of periodic leg movements in hospitalized heart failure patients. (2015)
  • Author(s): Kanno Y, Yoshihisa A, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] The association between plasma levels of anti-angiogenic isoform of vascular endothelial growth factor and clinical profiles of peripheral artery disease. (2015)
  • Author(s): Sato A, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] The CHA2DS2-VASc score predicts high mortality in hospitalized heart failure patients. (2015)
  • Author(s): Watanabe S, Yoshihisa A, Kanno Y, Takiguchi M, Miura S, Sato A, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Sakamoto N, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: Scientific Sessions of American Heart Association 2015
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-11-07 – 2015-11-11
  • Int'l Joint Research
• [Presentation] Association between hyperuricemia and mortality in heart failure patients with preserved ejection fraction (2015)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Takeishi Y.
  • Organizer: 第19回日本心不全学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-10-22 – 2015-10-24
• [Presentation] RCA入口部の高度石灰化亜完全閉塞に対しRotablatorが有効であった症例. (2015)
  • Author(s): 君島勇輔, 國井浩行, 肱岡奈保子, 中村裕一, 阿部諭史, 神山美之, 坂本信雄, 八巻尚洋, 中里和彦, 鈴木 均, 齋藤修一, 竹石恭知
  • Organizer: 第24回日本心血管インターベンション治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-07-30 – 2015-08-01
• [Presentation] 心不全患者における末梢動脈疾患の検討. (2015)
  • Author(s): 中村裕一, 國井浩行, 義久精臣, 清水竹史, 大和田卓史, 坂本信雄, 八巻尚洋, 杉本浩一, 中里和彦, 鈴木 均, 齋藤修一, 竹石恭知.
  • Organizer: 第24回日本心血管インターベンション治療学会
  • Place of Presentation: 福岡
  • Year and Date: 2015-07-30 – 2015-08-01
• [Presentation] Impact of serum uric acid on mortality in heart failure with preserved ejection fraction. (2015)
  • Author(s): Shimizu T, Yoshihisa A, Takiguchi M, Miura S, Nakamura Y, Owada T, Yamauchi H, Abe S, Suzuki S, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2016-04-26
• [Presentation] High mobility group box 1 promotes angiogenesis from bone marrow-derived endothelial progenitor cells after myocardial infarction (2015)
  • Author(s): Yuichi Nakamura, Satoshi Suzuki, Takeshi Shimizu, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Peripheral Artery Disease Predicts Adverse Prognosis of Heart Failure Patients (2015)
  • Author(s): Yuichi Nakamura, Akiomi Yoshihisa, Hiroyuki Kunii, Takeshi Shimizu, Hiroyuki Yamauchi, Satoshi Abe, Satoshi Suzuki, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Impact of body mass index on mortality in heart failure patients (2015)
  • Author(s): Takiguchi M, Yoshihisa A, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Sugimoto K, Yamaki T, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] mpact of hypocalcemia on mortality of patients with heart failure and chronic kidney disease (2015)
  • Author(s): Miura S, Yoshihisa A, Takiguchi M, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Impact of insomnia on prognosis in hospitalized heart failure patients (2015)
  • Author(s): Takiguchi M, Yoshihisa A, Miura S, Shimizu T, Nakamura Y, Yamauchi H, Owada T, Abe S, Suzuki S, Oikawa M, Kobayashi A, Yamaki T, Sugimoto K, Kunii H, Nakazato K, Suzuki H, Saitoh S, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Impact of peripheral artery disease on prognosis in patients with heart failure (2015)
  • Author(s): Yoshihisa A, Nakamura Y, Kunii H, Takeishi Y
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26
• [Presentation] Myocardial infarct size quantification in mice using pinhole single-photon emission computed tomography. (2015)
  • Author(s): Shimizu T, Nakamura Y, Suzuki S, Kubo H, Ito H, Shishido F, Takenoshita S, Takeishi Y.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2015-04-24 – 2015-04-26